Structural and signaling mechanisms of TAAR1 enabled preferential agonist design.

Trace amine-associated receptor 1 (TAAR1) senses a spectrum of endogenous amine-containing metabolites (EAMs) to mediate diverse psychological functions and is useful for schizophrenia treatment without the side effects of catalepsy. Here, we systematically profiled the signaling properties of TAAR1 activation and present nine structures of TAAR1-Gs/Gq in complex with EAMs, clinical drugs, and synthetic compounds. These structures not only revealed the primary amine recognition pocket (PARP) harboring the conserved acidic D3.32 for conserved amine recognition and "twin" toggle switch for receptor activation but also elucidated that targeting specific residues in the second binding pocket (SBP) allowed modulation of signaling preference. In addition to traditional drug-induced Gs signaling, Gq activation by EAM or synthetic compounds is beneficial to schizophrenia treatment. Our results provided a structural and signaling framework for molecular recognition by TAAR1, which afforded structural templates and signal clues for TAAR1-targeted candidate compounds design.

Changes in frailty and depressive symptoms among middle-aged and older Chinese people: a nationwide cohort study.

BACKGROUND AND AIMS: The older people bears a severe burden of disease due to frailty and depressive symptoms, however, the results of association between the two in the older Chinese people have been conflicting. Therefore, this study aimed to investigate the developmental trajectories and interactions of frailty and depressive symptoms in the Chinese middle-aged and older adults. METHODS: The study used four waves of data from 2011, 2013, 2015 and 2018 in the China Health and Retirement Longitudinal Study (CHARLS) database, focused on middle-aged and older people ≥ 45 years of age, and analyzed using latent growth models and cross-lagged models. RESULTS: The parallel latent growth model showed that the initial level of depressive symptoms had a significant positive predictive effect on the initial level of frailty. The rate of change in depressive symptoms significantly positively predicted the rate of change in frailty. The initial level of frailty had a significant positive predictive effect on the initial level of depressive symptoms, but a significant negative predictive effect on the rate of change in depressive symptoms. The rate of change in frailty had a significant positive predictive effect on the rate of change in depressive symptoms. The results of the cross-lagged analysis indicated a bidirectional causal association between frailty and depressive symptoms in the total sample population. Results for the total sample population grouped by age and gender were consistent with the total sample. CONCLUSIONS: This study recommends advancing the age of concern for frailty and depressive symptoms to middle-aged adults. Both men and women need early screening and intervention for frailty and depressive symptoms to promote healthy aging.

Research on the Interaction Mechanism and Structural Changes in Human Serum Albumin with Hispidin Using Spectroscopy and Molecular Docking.

The interaction between human serum albumin (HSA) and hispidin, a polyketide abundantly present in both edible and therapeutic mushrooms, was explored through multispectral methods, hydrophobic probe assays, location competition trials, and molecular docking simulations. The results of fluorescence quenching analysis showed that hispidin quenched the fluorescence of HSA by binding to it via a static mechanism. The binding of hispidin and HSA was validated further by synchronous fluorescence, three-dimensional fluorescence, and UV/vis spectroscopy analysis. The apparent binding constant (Ka) at different temperatures, the binding site number (n), the quenching constants (Ksv), the dimolecular quenching rate constants (Kq), and the thermodynamic parameters (∆G, ∆H, and ∆S) were calculated. Among these parameters, ∆H and ∆S were determined to be 98.75 kJ/mol and 426.29 J/(mol·K), respectively, both exhibiting positive values. This observation suggested a predominant contribution of hydrophobic forces in the interaction between hispidin and HSA. By employing detergents (SDS and urea) and hydrophobic probes (ANS), it became feasible to quantify alterations in Ka and surface hydrophobicity, respectively. These measurements confirmed the pivotal role of hydrophobic forces in steering the interaction between hispidin and HSA. Site competition experiments showed that there was an interaction between hispidin and HSA molecules at site I, which situates the IIA domains of HSA, which was further confirmed by the molecular docking simulation.

Advances in spatial transcriptomics and related data analysis strategies.

Spatial transcriptomics technologies developed in recent years can provide various information including tissue heterogeneity, which is fundamental in biological and medical research, and have been making significant breakthroughs. Single-cell RNA sequencing (scRNA-seq) cannot provide spatial information, while spatial transcriptomics technologies allow gene expression information to be obtained from intact tissue sections in the original physiological context at a spatial resolution. Various biological insights can be generated into tissue architecture and further the elucidation of the interaction between cells and the microenvironment. Thus, we can gain a general understanding of histogenesis processes and disease pathogenesis, etc. Furthermore, in silico methods involving the widely distributed R and Python packages for data analysis play essential roles in deriving indispensable bioinformation and eliminating technological limitations. In this review, we summarize available technologies of spatial transcriptomics, probe into several applications, discuss the computational strategies and raise future perspectives, highlighting the developmental potential.

Activation of CTNNB1 by deubiquitinase UCHL3-mediated stabilization facilitates bladder cancer progression.

BACKGROUND: The catenin beta 1 gene (CTNNB1) plays a crucial role in the malignant progression of various cancers. Recent studies have suggested that CTNNB1 hyperactivation is closely related to the occurrence and development of bladder cancer (BCa). As a member of the deubiquitinating enzyme (DUB) family, ubiquitin C-terminal hydrolase L3 (UCHL3) is abnormally expressed in various cancers. In this study, we discovered that UCHL3 is a novel oncogene in bladder cancer, suggesting it is a promising target against bladder cancer. METHODS: We utilized CRISPR‒Cas9 technology to construct cell lines with UCHL3 stably overexpressed or knocked out. The successful overexpression or knockout of UCHL3 was determined using Western blotting. Then, we performed CCK-8, colony formation, soft agar and Transwell migration assays to determine the impact of the UCHL3 gene on cell phenotype. RNA-seq was performed with UCHL3-depleted T24 cells (established via CRISPR-Cas9-mediated genomic editing). We analyzed differences in WNT pathway gene expression in wild-type and UCHL3-deficient T24 cell lines using a heatmap and by gene set enrichment analysis (GSEA). Then, we validated the effect of UCHL3 on the Wnt pathway using a dual fluorescence reporter. We then analyzed the underlying mechanisms involved using Western blots, co-IP, and immunofluorescence results. We also conducted nude mouse tumor formation experiments. Moreover, conditional UCHL3-knockout mice and bladder cancer model mice were established for research. RESULTS: We found that the overexpression of UCHL3 boosted bladder cancer cell proliferation, invasion and migration, while the depletion of UCHL3 in bladder cancer cells delayed tumor tumorigenesis in vitro and in vivo. UCHL3 was highly associated with the Wnt signaling pathway and triggered the activation of the Wnt signaling pathway, which showed that its functions depend on its deubiquitination activity. Notably, Uchl3-deficient mice were less susceptible to bladder tumorigenesis. Additionally, UCHL3 was highly expressed in bladder cancer cells and associated with indicators of advanced clinicopathology. CONCLUSION: In summary, we found that UCHL3 is amplified in bladder cancer and functions as a tumor promoter that enhances proliferation and migration of tumor cells in vitro and bladder tumorigenesis and progression in vivo. Furthermore, we revealed that UCHL3 stabilizes CTNNB1 expression, resulting in the activation of the oncogenic Wnt signaling pathway. Therefore, our findings strongly suggest that UCHL3 is a promising therapeutic target for bladder cancer.

Dyadic psycho-social interventions for stroke survivors and family caregivers: A systematic review and meta-analysis of randomized controlled trials.

AIMS AND OBJECTIVES: To describe dyadic psycho-social intervention measures and to evaluate their influence on stroke survivors and caregiver's functional independence, quality of life, depression, anxiety, self-efficacy and coping ability. BACKGROUND: Because of the importance of dyadic intervention and the seriousness of the psycho-social problems of stroke survivors and caregivers, understanding the influence of dyadic psycho-social interventions is vital. DESIGN: A systematic review and meta-analysis based on PRISMA guidelines. DATA SOURCES: Nine databases were systematically searched for randomized controlled trials submitted from 1910 to 4 July 2022. METHODS: The included papers were evaluated for quality, and quantitative data were standardly extracted and analysed by meta-analysis, followed by synthesis. The meta-analysis was carried out using Review Manager 5.4 software. RESULTS: Fifteen randomized controlled trials were included (n = 2190 for patients, and n = 1933 for caregivers). Study results showed that dyadic psycho-social interventions significantly alleviated the depressive symptoms of patients, obviously improved the ability to function independently of patients and more quickly alleviated the care burden of caregivers. CONCLUSIONS: This study provided moderate support for the benefits of dyadic psycho-social intervention in improving survivor and caregiver's functional independence, quality of life, depression, anxiety, self-efficacy and care burden. Nevertheless, due to limitations of the study, it was deemed necessary that this topic is studied further. RELEVANCE TO CLINICAL PRACTICE: This review suggests that dyadic psycho-social interventions should be considered as effective strategies for decreasing psycho-social problems of stroke survivors and caregivers, and provides evidence for the formulation of targeted intervention programs. The personalized implementation of such interventions should be the focus of clinical practice. NO PATIENT OR PUBLIC CONTRIBUTION: There was no patient or public contribution.

The construction of an artificial light-harvesting system with two-step sequential energy transfer based on supramolecular polymers.

An artificial light-harvesting system with two-step sequential energy transfer was constructed in aqueous media based on cyano-substituted p-phenylenevinylene derivative (PPTA) and bis-(p-sulfonatocalix[4]arenes) (BSC4) supramolecular polymers formed through host-guest interactions, in which two different fluorescent dyes, eosin Y (EY) and sulforhodamine (SR101), were employed as energy acceptors. The obtained artificial light-harvesting system can achieve an efficient two-step energy transfer process from PPTA-BSC4 to EY and then to SR101 with high energy-transfer efficiencies of up to 36.6% and 40.8%, respectively. More importantly, the harvested energy from the PPTA-BSC4 + EY + SR101 system can be used to promote the dehalogenation of α-bromoacetophenone with a yield of 89% in aqueous solution.

Confined Heteropoly Blues in Defected Zr-MOF (Bottle Around Ship) for High-Efficiency Oxidative Desulfurization.

The Keggin-type polyoxometalates (POMs) are effective catalysts for oxidative desulfurization (ODS) and confining these POMs in metal-organic frameworks (MOFs) is a promising strategy to improve their performances. Herein, postsynthetic modification of POMs confined in MOFs by adding thiourea creates more unsaturated metal sites as defects, promoting ODS catalytic activity. Additional modification by confining 1-butyl-3-methyl imidazolium POMs in MOFs is performed to obtain higher ODS activity, owing to the affinity between electron-rich thiophene-based compounds and electrophilic imidazolium compounds. The ODS catalytic activities of four Zr-MOF-based composites (bottle around ship) including phosphomolybdate acid (PMA)/UiO-66, [Bmim]3 PMo12 O40 /UiO-66, PMA/Thiourea/UiO-66, and [Bmim]3 PMo12 O40 /Thiourea/UiO-66 are therefore investigated in detail. In order to explore the catalytic mechanism of these MOF composites, their microstructures and electronic structures are probed by various techniques such as X-ray diffraction, thermogravimetric analysis, Fourier transform infrared, Raman, scanning electron microscope, transmission electron microscope, BET, X-ray photoelectron spectroscopy, EPR, UV-vis, NMR spectra, and H2 -temperature-programmed reduction. The results reveal that phosphomolybdate blues and imidazolium phosphomolybdate blues with different Mo5+ /Mo6+ ratios with the Keggin structure are confined in defected UiO-66 for all four composites. This approach can be applied to design and synthesize other POMs/MOFs composites as efficient catalysts.

Synergistic Effect between Zr-MOF and Phosphomolybdic Acid with the Promotion of TiF4 Template.

Metal-Organic Framework (MOF) materials are often modified or functionalized, and then the crystal size and morphology of MOF materials are changed. In the process of preparing UiO-66 confined phosphomolybdic acid (PMA) composites (PU), the TiF4-modified PU (PMA + UiO-66) composite catalyst (TiF4-PU) was successfully synthesized by adding titanium tetrafluoride, and the catalytic desulfurization activity was excellent. Similarly, the reaction mechanism was investigated by means of infrared spectroscopy, Raman spectroscopy, XPS, and UV/Vis spectroscopy. The results show that the addition of TiF4 not only changes the appearance and color of the catalyst, but also changes the valence distribution of the elements in the catalyst. The number of oxygen vacancies in the MOF increases due to the addition of TiF4, and more electrons are transferred from the Zr-MOF to PMA to form more Mo5+, which improved the performance of oxidative desulfurization in comparison. Thus, a stronger strong metal-support interaction (SMSI) effect is observed for TiF4-modified PU catalysts. In addition, the quenching experiment of free radicals shows that ·OH radical is the main active substance in the oxidative desulfurization reaction over TiF4-PU catalyst.

Impact of repeat HER2 testing after initial equivocal HER2 FISH results using 2013 ASCO/CAP guidelines.

PURPOSE: The updated 2013 American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 (HER2) testing have made some major changes in HER2 fluorescence in situ hybridization (FISH) interpretation criteria with additional FISH equivocal cases. Repeat HER2 testing is recommended after initial HER2 FISH equivocal results; however, little is known about its impact on final HER2 status. The aim of this study is to investigate whether reflex test clarifies HER2 status, and to characterize clinicopathological features of the newly defined HER2 equivocal group. METHODS: A total of 886 consecutive cases of primary invasive breast cancer conducted with dual-probe HER2 FISH testing between November 2013 and December 2015 were reviewed. HER2 immunohistochemistry (IHC) and FISH testing were performed on a different tissue block or a new specimen after initial HER2 FISH equivocal results. RESULTS: Compared to 2007 guideline, 85 (9.6%) cases changed their category by using 2013 guideline. The major change of the 85 cases is that 57 (6.4%) cases in HER2 FISH-negative category changed to equivocal, and the equivocal category cases increased from 36 to 67. HER2 FISH equivocal was significantly associated with HER2 IHC equivocal (2+) and chromosome 17 polysomy (P < 0.01). Repeat testing by IHC and FISH clarified HER2 status in 33 and 42% of HER2 equivocal cases, respectively. Overall 32 (48%) initial HER2 equivocal cases stayed HER2 equivocal after repeat FISH and or IHC testing. These tumors were ER/PR+, with high KI-67 index. CONCLUSION: New guidelines classify more HER2 FISH equivocal cases. Repeat HER2 testing clarifies HER2 status in about 50% of initial HER2 FISH equivocal cases. In addition, HER2 equivocal cases merit further study as there is limited information about prognosis and optimal treatment strategy for this population.

Investigation of correlation between mutational status in key EGFR signaling genes and prognosis of stage II colorectal cancer.

AIM: To investigate the relationship between mutations of key genes in the EGFR signaling pathway and the prognosis of stage II colorectal cancer patients without chemotherapy. MATERIALS & METHODS: The incidence of KRAS, NRAS, BRAF, PIK3CA mutations and deficient DNA mismatch repair were assessed in 160 stage II colorectal cancer patients who had been treated by radical operation without adjuvant chemotherapy. RESULTS: Mutations in KRAS, BRAF or PIK3CA were associated with poor prognosis, while the deficient DNA mismatch repair status was not associated with the prognosis. Combining these three markers, the sensitivity of the predicted value for poor progression-free survival and overall survival reached 0.645 (p = 0.002) and 0.709 (p = 0.001), respectively. CONCLUSION: Knowing the mutation status of KRAS, BRAF or PIK3CA in stage II colorectal cancer can significantly improve the accuracy of prognoses.

[Effect of Cordyceps sinensis powder on renal oxidative stress and mitochondria functions in 5/6 nephrectomized rats].

OBJECTIVE: To observe the effect of Cordyceps sinensis (CS) powder on renal oxidative stress and mitochondria functions in 5/6 nephrectomized rats, and to primarily explore its possible mechanisms. METHODS: Totally 30 male Sprague-Dawley rats were divided into the sham-operation group, the model group, and the treatment group by random digit table, 10 in each group. A chronic kidney disease (CKD) rat model was prepared by one step 5/6 nephrectomy. Rats in the treatment group were intragastrically administered with CS powder solution at the daily dose of 2 g/kg, once per day. Equal volume of double distilled water was intragastrically administered to rats in the sham-operation group and the model group. All medication lasted for 12 weeks. The general condition of rats, their body weight, blood pressure, 24 h proteinuria, urinary N-acetyl-ß-D-glucosaminidase (NAG), serum creatinine (SCr) , and blood urea nitrogen (BUN) were assessed before surgery, at week 2, 4, 6, 8, 10, and 10 after surgery. Pathological changes of renal tissues were observed under light microscope. Morphological changes of mitochondria in renal tubular epithelial cells were observed under transmission electron microscope. Activities of antioxidant enzymes including reduced glutathione (GSH), manganese superoxide dismutase (MnSOD), and malondialdehyde (MDA) in fresh renal tissue homogenate were detected. Mitochondria of renal tissues were extracted to detect levels of mitochondrial membrane potential and changes of reactive oxygen species (ROS). And expressions of cytochrome-C (Cyto-C) and prohibitin in both mitochondria and cytoplasm of the renal cortex were also measured by Western blot. RESULTS: (1) Compared with the sham-operation group, body weight was significantly decreased at week 2 (P <0. 01), but blood pressure increased at week 4 (P <0. 05) in the model group. Compared with the model group, body weight was significantly increased at week 12 (P <0. 01), but blood pressure decreased at week 8 (P < 0. 01) in the treatment group. (2) Compared with the sham-operation group, 24 h proteinuria, urinary NAG, blood SCr and BUN significantly increased in the model group (all P <0. 01). Compared with the model group, blood and urinary biochemical indices all significantly decreased in the treatment group (all P <0. 01). (3) Results of pathological renal scoring: Glomerular sclerosis index, scoring for tubulointerstitial fibrosis, degree of tubulointerstitial inflammatory infiltration were all obviously higher in the model group than in the sham-operation group (all P <0. 01). All the aforesaid indices were more obviously improved in the treatment group than in the model group (all P <0. 01). (4) Compared with the sham-operation group, activities of MnSOD and GSH-Px were significantly reduced, but MDA contents obviously increased in the renal cortex of the model group (all P <0. 01). Compared with the model group, activities of MnSOD and GSH-Px obviously increased (P <0. 05, P <0. 01), but MDA contents obviously decreased in the renal cortex of the treatment group (P <0. 01). (5) Compared with the sham-operation group, the mitochondrial membrane potential significantly decreased, but ROS levels significantly increased in the model group (all P <0.01). Compared with the model group, mitochondrial transmembrane potential increased in the treatment group, thereby inhibiting the tendency of increased production of ROS (both P < 0. 01). (6) Results of Western blot showed that, compared with the sham-operation group, expression levels of mitochondrial Cyto-C and Prohibitin were significantly reduced in the renal cortex (P <0. 01), but significantly elevated in the cytoplasm of the model group (P <0. 01). Compared with the model group, each index was obviously improved in the treatment group with statistical difference (P <0. 05, P <0. 01). CONCLUSION: CS powder had renal protection, and its mechanism might partially depend on in- hibition of oxidative stress and protection for mitochondria.

The causal relationship between sleep disturbances and the risk of frailty: a two-sample Mendelian randomization study.

OBJECTIVE: Adequate sleep is closely related to people's health. However, with increasing age, the quality of sleep worsens. At the same time, among elderly individuals, frailty is also a disturbing factor, which makes elderly individuals more vulnerable to negative factors. To explore the relationship between the two, we conducted this study. METHODS: In this paper, independent genetic variations related to insomnia, sleep duration and daytime sleepiness were selected as IVs, and related genetic tools were used to search published genome-wide association studies for a two-sample Mendelian randomization (TSMR) analysis. The inverse-variance weighted (IVW) method was used as the main Mendelian randomization analysis method. Cochran's Q test was used to test heterogeneity, MR‒Egger was used to test horizontal pleiotropy, and the MR-PRESSO test was used to remove outliers. RESULTS: According to our research, insomnia (OR = 1.10, 95% CI 1.03-1.17, P = 2.59e-97), long sleep duration (OR = 0.66, 95% CI 0.37-1.17, P = 0.02), short sleep duration (OR = 1.30, 95% CI 1.22-1.38, P = 2.23e-17) and daytime sleepiness (OR = 1.49, 95% CI 1.25-1.77, P = 0.96e-4) had a bidirectional causal relationship with frailty. CONCLUSIONS: Our research showed that there is a causal relationship between sleep disturbances and frailty. This result was obtained by a TSMR analysis, which involves the use of genetic variation as an IV to determine causal relationships between exposure and outcome. Future TSMR studies should include a larger sample for analysis.

Pirfenidone inhibits macrophage infiltration in 5/6 nephrectomized rats.

Tubulointerstitial macrophage infiltration is a hallmark of chronic kidney disease involved in the progression of renal fibrosis. Pirfenidone is a newly identified antifibrotic drug, the potential mechanism of which remains unclear. The aim of this study was to investigate the effects of pirfenidone on M1/M2 macrophage infiltration in nephrectomized rats. Nephrectomized rats were treated with pirfenidone by gavage for 12 wk. Twenty-four hour urinary protein, N-acetyl-ß-D-glycosaminidase (NAG) activity, systolic blood pressure, and C-reactive protein were determined. Paraffin-embedded sections were stained for CD68, CCR7, and CD163 macrophages. Monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-1α (MIP-1α), as well as M1 and M2 macrophages secretory markers, were evaluated by real-time RT-PCR and Western blotting analysis. Pirfenidone significantly improved the elevated proteinuria and NAG activity from week 2 onward after surgery. Pirfenidone attenuated interstitial fibrosis and decreased expression of fibrotic markers including transforming growth factor-ß(1), connective tissue growth factor, α-smooth muscle actin, fibronectin, and fibroblast-specific protein-1. Pirfenidone significantly decreased the infiltrating macrophages. The number of M1 and M2 macrophages was significantly lower after pirfenidone treatment. MCP-1 and MIP-1α were increased in nephrectomized rats at mRNA and protein levels. Pirfenidone treatment significantly inhibited their expression. The TNF-α, IL-6, and nitric oxide synthases-2 expressed by M1 macrophages were increased in nephrectomized rats, and pirfenidone significantly attenuated their expression. Pirfenidone treatment also significantly decreased arginase-1, dectin-1, CD206, and CD86 expressed by M2 macrophages. Thus pirfenidone inhibits M1 and M2 macrophage infiltration in 5/6 nephrectomized rats, which suggests its efficacy in the early and late periods of renal fibrosis.

FTY720 attenuates tubulointerstitial inflammation and fibrosis in subtotally nephrectomized rats.

Tubulointerstitial fibrosis is a common pathway that leads to kidney failure, and persistent tubulointerstitial inflammation is a key event in the development of tubulointerstitial fibrosis. The new immunosuppressive drug FTY720 modifies lymphocyte migration into injured tissues by sequestering lymphocytes within secondary lymphoid organs. However, its therapeutic effect on tubulointerstitial inflammation and fibrosis had not been well understood. This study was designed to explore the effect of FTY720 on tubulointerstitial inflammation and fibrosis in subtotally nephrectomized (SNX) rats. In total, 24 male Sprague-Dawley rats were used. Seven days after 5/6 nephrectomy, rats were randomized to FTY720 (1 mg/kg/d) and placebo-treated groups. Sham-operated rats served as controls. FTY720 significantly attenuated the rise in proteinuria, serum creatinine, urea nitrogen and N-acetyl-ß-D-glucosaminidase activity in SNX rats, and reduced the count of peripheral white blood cells and lymphocytes in SNX rats. Morphological analysis revealed that there was severe tubulointerstitial inflammation and fibrosis in SNX group and much more tubulointerstitial infiltrating inflammatory cells with high expression of CD3, CD4, CD8, CD20, CD68, CD163 and CCR-7 in SNX group, as compared with the controls, but the lesions were attenuated significantly by treatment with FTY720. Furthermore, the expressions of proinflammatory molecules (IL-6, TNF-α and MCP-1), profibrotic molecule (TGF-ß1) and production of extracellular matrix proteins such as fibronectin and types I and III collagens were upregulated in SNX rats. FTY720 administration significantly reduced these abnormalities. In summary, FTY720 exerts therapeutic effects on tubulointerstitial fibrosis in SNX rats by inhibiting the tubulointerstitial inflammatory response.

Ammonium 2-(3,4-di-methyl-benzo-yl)benzoate dihydrate.

In the anion of the title compound, NH4 (+)·C16H13O3 (-)·2H2O, the benzene rings are twisted with respect to each other by 73.56 (10)°. In the crystal, extensive N-H⋯O and O-H⋯O hydrogen bonds link the cations, anions and lattice water mol-ecules into a three dimensional supra-molecular structure.

(2,2'-Bi-pyridine-κ(2) N,N')bis-(nitrato-κ(2) O,O')copper(II).

In the title complex, [Cu(NO3)2(C10H8N2)], the Cu(II) cation is chelated by two nitrate anions and by one 2,2'-bi-pyridine ligand in a distorted N2O4 octa-hedral geometry. The dihedral angle between the pyridine rings is 1.92 (11)°. In the crystal, π-π stacking between parallel pyridine rings of adjacent complex mol-ecules is observed, the centroid-centroid distance being 3.6788 (19) Å. Weak C-H⋯O hydrogen bonds further link the mol-ecules into a three-dimensional supra-molecular architecture.

[Fingerprint research on immunosuppressive fraction of Rehmanniae Radix by HPLC].

OBJECTIVE: To study the HPLC fingerprint of immunosuppressive fraction of Rehmanniae Radix, the genuine medicinal materials in Henan province. METHODS: By HPLC method,Dikma Platisil-C18 column (250 mm x 4.6 mm, 5 microm) was used with acetonitrile-0.1% phosphoric acid as mobile phase by gradient elution. The detection wavelength was 210 nm, flow rate was 1.0 mL/min and column temperature was set at 30 degrees C. RESULTS: Compared the 10 batches sample of the fingerprint similarity, 18 common peaks were marked and five peaks were identified. The similarities were more than 0.9. CONCLUSION: HPLC fingerprint of immunosuppressive fraction of Rehmanniae Radix is established, which lays the foundation for further pharmacodynamics research on Rehmanniae Radix.

Bilateral Peutz-Jeghers-Associated Sex Cord Tumor With Annular Tubules Combined With Unilateral Adult Granulosa Cell Tumor: A Case Report.

Sex cord tumor with annular tubules (SCTATs) is a rare sex cord stromal tumor in the ovary. SCTAT combined with adult granulosa cell tumor (AGCT) is even rarer. Here, we report a unique case of ovarian tumors with mixed AGCT and SCTAT components. Due to the unusual coexistence, molecular testing was separately performed on each ovary. Both SCTAT and AGCT components were found to have STK11 germline mutation. Furthermore, the AGCT component had an additional FOXL2 somatic mutation. Based on medical history and molecular testing we conclude that the ovarian tumors were associated with Peutz-Jeghers syndrome (PJS). Thus, we present the first report of bilateral PJS-associated SCTAT combined with unilateral AGCT.