Structural Mechanism for GSDMD Targeting by Autoprocessed Caspases in Pyroptosis.

The pyroptosis execution protein GSDMD is cleaved by inflammasome-activated caspase-1 and LPS-activated caspase-11/4/5. The cleavage unmasks the pore-forming domain from GSDMD-C-terminal domain. How the caspases recognize GSDMD and its connection with caspase activation are unknown. Here, we show site-specific caspase-4/11 autoprocessing, generating a p10 product, is required and sufficient for cleaving GSDMD and inducing pyroptosis. The p10-form autoprocessed caspase-4/11 binds the GSDMD-C domain with a high affinity. Structural comparison of autoprocessed and unprocessed capase-11 identifies a ß sheet induced by the autoprocessing. In caspase-4/11-GSDMD-C complex crystal structures, the ß sheet organizes a hydrophobic GSDMD-binding interface that is only possible for p10-form caspase-4/11. The binding promotes dimerization-mediated caspase activation, rendering a cleavage independently of the cleavage-site tetrapeptide sequence. Crystal structure of caspase-1-GSDMD-C complex shows a similar GSDMD-recognition mode. Our study reveals an unprecedented substrate-targeting mechanism for caspases. The hydrophobic interface suggests an additional space for developing inhibitors specific for pyroptotic caspases.

Structural mechanisms for regulation of GSDMB pore-forming activity.

Cytotoxic lymphocyte-derived granzyme A (GZMA) cleaves GSDMB, a gasdermin-family pore-forming protein1,2, to trigger target cell pyroptosis3. GSDMB and the charter gasdermin family member GSDMD4,5 have been inconsistently reported to be degraded by the Shigella flexneri ubiquitin-ligase virulence factor IpaH7.8 (refs. 6,7). Whether and how IpaH7.8 targets both gasdermins is undefined, and the pyroptosis function of GSDMB has even been questioned recently6,8. Here we report the crystal structure of the IpaH7.8-GSDMB complex, which shows how IpaH7.8 recognizes the GSDMB pore-forming domain. We clarify that IpaH7.8 targets human (but not mouse) GSDMD through a similar mechanism. The structure of full-length GSDMB suggests stronger autoinhibition than in other gasdermins9,10. GSDMB has multiple splicing isoforms that are equally targeted by IpaH7.8 but exhibit contrasting pyroptotic activities. Presence of exon 6 in the isoforms dictates the pore-forming, pyroptotic activity in GSDMB. We determine the cryo-electron microscopy structure of the 27-fold-symmetric GSDMB pore and depict conformational changes that drive pore formation. The structure uncovers an essential role for exon-6-derived elements in pore assembly, explaining pyroptosis deficiency in the non-canonical splicing isoform used in recent studies6,8. Different cancer cell lines have markedly different isoform compositions, correlating with the onset and extent of pyroptosis following GZMA stimulation. Our study illustrates fine regulation of GSDMB pore-forming activity by pathogenic bacteria and mRNA splicing and defines the underlying structural mechanisms.

A GPR174-CCL21 module imparts sexual dimorphism to humoral immunity.

Humoral immune responses to immunization and infection and susceptibilities to antibody-mediated autoimmunity are generally lower in males1-3. However, the mechanisms underlying such sexual dimorphism are not well understood. Here we show that there are intrinsic differences between the B cells that produce germinal centres in male and female mice. We find that antigen-activated male B cells do not position themselves as efficiently as female B cells in the centre of follicles in secondary lymphoid organs, in which germinal centres normally develop. Moreover, GPR174-an X-chromosome-encoded G-protein-coupled receptor-suppresses the formation of germinal centres in male, but not female, mice. This effect is intrinsic to B cells, and correlates with the GPR174-enhanced positioning of B cells towards the T-cell-B-cell border of follicles, and the distraction of male, but not female, B cells from S1PR2-driven follicle-centre localization. Biochemical fractionation of conditioned media that induce B-cell migration in a GPR174-dependent manner identifies CCL21 as a GPR174 ligand. In response to CCL21, GPR174 triggers a calcium flux and preferentially induces the migration of male B cells; GPR174 also becomes associated with more Gαi protein in male than in female B cells. Male B cells from orchidectomized mice exhibit impaired GPR174-mediated migration to CCL21, and testosterone treatment rescues this defect. Female B cells from testosterone-treated mice exhibit male-like GPR174-Gαi association and GPR174-mediated migration. Deleting GPR174 from male B cells causes more efficient positioning towards the follicular centre, the formation of more germinal centres and an increased susceptibility to B-cell-dependent experimental autoimmune encephalomyelitis. By identifying GPR174 as a receptor for CCL21 and demonstrating its sex-dependent control of B-cell positioning and participation in germinal centres, we have revealed a mechanism by which B-cell physiology is fine-tuned to impart sexual dimorphism to humoral immunity.

Optimizing oxygen vacancies through grain boundary engineering to enhance electrocatalytic nitrogen reduction.

Electrocatalytic nitrogen reduction is a challenging process that requires achieving high ammonia yield rate and reasonable faradaic efficiency. To address this issue, this study developed a catalyst by in situ anchoring interfacial intergrown ultrafine MoO2 nanograins on N-doped carbon fibers. By optimizing the thermal treatment conditions, an abundant number of grain boundaries were generated between MoO2 nanograins, which led to an increased fraction of oxygen vacancies. This, in turn, improved the transfer of electrons, resulting in the creation of highly active reactive sites and efficient nitrogen trapping. The resulting optimal catalyst, MoO2/C700, outperformed commercial MoO2 and state-of-the-art N2 reduction catalysts, with NH3 yield and Faradic efficiency of 173.7 µg h-1 mg-1cat and 27.6%, respectively, under - 0.7 V vs. RHE in 1 M KOH electrolyte. In situ X-ray photoelectron spectroscopy characterization and density functional theory calculation validated the electronic structure effect and advantage of N2 adsorption over oxygen vacancy, revealing the dominant interplay of N2 and oxygen vacancy and generating electronic transfer between nitrogen and Mo(IV). The study also unveiled the origin of improved activity by correlating with the interfacial effect, demonstrating the big potential for practical N2 reduction applications as the obtained optimal catalyst exhibited appreciable catalytic stability during 60 h of continuous electrolysis. This work demonstrates the feasibility of enhancing electrocatalytic nitrogen reduction by engineering grain boundaries to promote oxygen vacancies, offering a promising avenue for efficient and sustainable ammonia production.

Research progress on anti-tumor mechanisms of scutellarin.

Scutellarin, one of natural flavonoids from Scutellaria barbata D. Don and Erigeron breviscapus (vant) Hand.-Mazz. Modern pharmacological studies have shown that scutellarin has a good anti-tumor effect. According to the literature review at home and abroad, scutellarin can inhibit the growth and metastasis of tumor cells, block the cell cycle at various stages, induce apoptosis and autophagy, interfere with tumor metabolism, reverse drug resistance of tumor cells and enhance the sensitivity of chemotherapy drugs. In this paper, the anti-tumor mechanism of scutellarin was reviewed, and the shortcomings of current studies and future research directions were analyzed, so as to provide a basis for further exploration of the anti-tumor potential of scutellarin and its further development and utilization.

Identification and Functional Analysis of Drought-Responsive Long Noncoding RNAs in Maize Roots.

Long noncoding RNAs (lncRNAs) are transcripts with lengths of more than 200 nt and limited protein-coding potential. They were found to play important roles in plant stress responses. In this study, the maize drought-tolerant inbred line AC7643 and drought-sensitive inbred line AC7729/TZSRW, as well as their recombinant inbred lines (RILs) were selected to identify drought-responsive lncRNAs in roots. Compared with non-responsive lncRNAs, drought-responsive lncRNAs had different sequence characteristics in length of genes and number of exons. The ratio of down-regulated lncRNAs induced by drought was significantly higher than that of coding genes; and lncRNAs were more widespread expressed in recombination sites in the RILs. Additionally, by integration of the modifications of DNA 5-methylcytidine (5mC), histones, and RNA N6-methyladenosine (m6A), it was found that the enrichment of histone modifications associated with transcriptional activation in the genes generated lncRNAs was lower that coding genes. The lncRNAs-mRNAs co-expression network, containing 15,340 coding genes and 953 lncRNAs, was constructed to investigate the molecular functions of lncRNAs. There are 13 modules found to be associated with survival rate under drought. We found nine SNPs located in lncRNAs among the modules associated with plant survival under drought. In conclusion, we revealed the characteristics of lncRNAs responding to drought in maize roots based on multiomics studies. These findings enrich our understanding of lncRNAs under drought and shed light on the complex regulatory networks that are orchestrated by the noncoding RNAs in response to drought stress.

Peak oxygen uptake is a strong prognostic predictor for pulmonary hypertension due to left heart disease.

BACKGROUND: Pulmonary hypertension in left heart disease (PH-LHD), which includes combined post- and precapillary PH (Cpc-PH) and isolated postcapillary PH (Ipc-PH), differs significantly in prognosis. We aimed to assess whether cardiopulmonary exercise testing (CPET) predicts the long-term survival of patients with PH-LHD. METHODS: A single-center observational cohort enrolled 89 patients with PH-LHD who had undergone right heart catherization and CPET (mean pulmonary arterial pressure > 20 mm Hg and pulmonary artery wedge pressure ≥ 15 mm Hg) between 2013 and 2021. A receiver operating characteristic curve was plotted to determine the cutoff value of all-cause death. Survival was estimated using the Kaplan-Meier method and analyzed using the log-rank test. The Cox proportional hazards model was performed to determine the association between CPET and all-cause death. RESULTS: Seventeen patients died within a mean of 2.2 ± 1.3 years. Compared with survivors, nonsurvivors displayed a significantly worse 6-min walk distance, workload, exercise time and peak oxygen consumption (VO2)/kg with a trend of a lower oxygen uptake efficiency slope (OUES) adjusted by Bonferroni's correction. Multivariate Cox regression revealed that the peak VO2/kg was significantly associated with all-cause death after adjusting for Cpc-PH/Ipc-PH. Compared with Cpc-PH patients with a peak VO2/kg ≥ 10.7 ml kg-1 min-1, Ipc-PH patients with a peak VO2/kg < 10.7 ml kg-1 min-1 had a worse survival (P < 0.001). CONCLUSIONS: The peak VO2/kg is independently associated with all-cause death in patients with PH-LHD. The peak VO2/kg can also be analyzed together with Cpc-PH/Ipc-PH to better indicate the prognosis of patients with PH-LHD.

Machine Learning-Assisted Synchronous Fluorescence Sensing Approach for Rapid and Simultaneous Quantification of Thiabendazole and Fuberidazole in Red Wine.

Rapid analysis of components in complex matrices has always been a major challenge in constructing sensing methods, especially concerning time and cost. The detection of pesticide residues is an important task in food safety monitoring, which needs efficient methods. Here, we constructed a machine learning-assisted synchronous fluorescence sensing approach for the rapid and simultaneous quantitative detection of two important benzimidazole pesticides, thiabendazole (TBZ) and fuberidazole (FBZ), in red wine. First, fluorescence spectra data were collected using a second derivative constant-energy synchronous fluorescence sensor. Next, we established a prediction model through the machine learning approach. With this approach, the recovery rate of TBZ and FBZ detection of pesticide residues in red wine was 101% ± 5% and 101% ± 15%, respectively, without resorting complicated pretreatment procedures. This work provides a new way for the combination of machine learning and fluorescence techniques to solve the complexity in multi-component analysis in practical applications.

Research progress of natural products interfering with cell signaling pathway in liver fibrosis.

Liver cirrhosis and hepatocellular carcinoma are the late stage of liver fibrosis. How to early use drugs to intervene in liver fibrosis is a prerequisite for the reversal of liver fibrosis. This paper mainly introduces a cell signaling transduction pathway in liver fibrosis and the intervention of natural products in order to provide theoretical basis for the treatment of liver fibrosis.

The structure of blood-tumor barrier and distribution of chemotherapeutic drugs in non-small cell lung cancer brain metastases.

BACKGROUND: Brain metastasis is an important cause of increased mortality in patients with non-small cell lung cancer (NSCLC). In brain metastasis, the blood-brain barrier (BBB) is frequently impaired, forming blood-tumor barrier (BTB). The efficacy of chemotherapy is usually very poor. However, the characteristics of BTB and the impacts of BTB on chemotherapeutic drug delivery remain unclear. The present study investigated the structure of BTB, as well as the distribution of routine clinical chemotherapeutic drugs in both brain and peripheral tumors. METHODS: Bioluminescent image was used to monitor the tumor load after intracranial injection of lung cancer Lewis cells in mice. The permeability of BBB and BTB was measured by fluorescent tracers of evans blue and fluorescein sodium. Transmission electron microscopy (TEM), immunohistochemistry and immunofluorescence were performed to analyze structural differences between BBB and BTB. The concentrations of chemotherapeutic drugs (gemcitabine, paclitaxel and pemetrexed) in tissues were assayed by liquid chromatography with tandem mass spectrometry (LC-MS/MS). RESULTS: Brain metastases exhibited increased BTB permeability compared with normal BBB detected by fluorescence tracers. TEM showed abnormal blood vessels, damaged endothelial cells, thick basement membranes, impaired intercellular endothelial tight junctions, as well as increased fenestrae and pinocytotic vesicles in metastatic lesions. Immunohistochemistry and immunofluorescence revealed that astrocytes were distributed surrounded the blood vessels both in normal brain and the tumor border, but no astrocytes were found in the inner metastatic lesions. By LC-MS/MS analysis, gemcitabine showed higher permeability in brain metastases. CONCLUSIONS: Brain metastases of lung cancer disrupted the structure of BBB, and this disruption was heterogeneous. Chemotherapeutic drugs can cross the BTB of brain metastases of lung cancer but have difficulty crossing the normal BBB. Among the three commonly used chemotherapy drugs, gemcitabine has the highest distribution in brain metastases. The permeability of chemotherapeutic agents is related to their molecular weight and liposolubility.

The levels of phthalate exposure and associations with obesity in an elderly population in China.

BACKGROUND: Few epidemiological studies on the correlation between phthalate exposure and elderly obesity in China are available. The purpose of the present study is to assess phthalate exposure levels and explore the connections between exposure to phthalates and obesity using a sample of Chinese community-dwelling elderly individuals. METHODS: Data were acquired from the baseline survey of the Cohort of Health of Elderly and Controllable Factors of Environment, which was established in Lu'an, Anhui province, China, from June to September in 2016. Urine samples were obtained to analyze the concentrations of seven phthalate metabolites, utilizing a high-performance liquid chromatography-tandem mass spectrometry method. General obesity was determined based on body mass index, and abdominal obesity based on waist circumference. Binary logistic regression models were utilized to analyze the associations of creatinine-corrected phthalate metabolite concentrations (categorized into quartiles) with general and abdominal obesity in elderly people. Moreover, a stratified analysis was performed to explore the difference between genders. RESULTS: Of 942 elderly individuals, 52.9% were defined as generally obese and 75.5% as abdominally obese. The detection rates of seven phthalate metabolites ranged from 90.07% to 99.80%. The highest median concentration was 44.08 µg/l (for MBP), and the lowest was 0.55 µg/l (for MEHP). The level of exposure to LMW(low-molecular-weight) PAEs is higher than that to HMW(high-molecular-weight) PAEs. After adjustment for confounding variables, we found a significant association between urinary MEOHP (mono-2-ethyl-5-oxohexyl phthalate), MEHP (mono-2-ethylhexyl phthalate), MBP (mono-n-butyl phthalate), MEP (mono-ethyl phthalate), and MMP (mono-methyl phthalate) levels and general obesity. MBP levels were also correlated with abdominal obesity. When stratified by gender, higher urinary levels of MEOHP, MBP, MEP, and MMP were associated with general obesity in males, whereas MBP and MMP levels were eminently correlated with general obesity in females. Higher urinary MBP levels were associated with increased abdominal obesity rates in males, but not in females. CONCLUSIONS: In conclusion, higher phthalate metabolite concentrations were correlated with obesity in the elderly. Moreover, a gender difference was observed in these associations.

The Therapeutic Effects of Endovascular Therapy with mTICI2b and 3 Recanalization for Acute Anterior Circulation Stroke Patients.

BACKGROUND AND PURPOSE: Modified Thrombolysis in Cerebral Infarction (mTICI)2b/3 has been considered the criterion for successful reperfusion in endovascular treatment. This study aimed to compare the therapeutic safety and efficacy of mTICI2b and mTICI3 recanalization, and to analyze the factors related to outcomes in everyday clinical practice. MATERIALS AND METHODS: This is a single-center retrospective analysis of 224 patients who underwent successful thrombectomy (achieving a mTICI score ≥2b). The primary outcomes included a modified Rankin score (mRS) of 0-2 at 90-day, mortality, and symptomatic intracranial hemorrhage. RESULTS: A total of 111 patients achieved mTICI2b status (49.6%), and 113 achieved mTICI3 status (50.4%). The comparison between mTICI2b and 3 reperfusions showed no differences in short-term outcomes, 90-day mRS, complications, and mortality. There was a trend toward more passes in mTICI2b patients, although the difference was not significant. The univariate analysis showed that poor outcomes after endovascular treatment were associated with older age, previous history of coronary heart disease, atrial fibrillation, diabetes, tandem occlusions, high National Institutes of Health Stroke Scale (NIHSS) score on admission, and general anesthesia. A previous history of coronary heart disease, a high NIHSS score on admission, and the use of general anesthesia were independent factors that affected the therapeutic effects. CONCLUSION: The superiority (efficacy and safety) of mTICI3 reperfusion was not significant compared with that of mTICI2b reperfusion. Prolonged efforts to achieve mTICI3 after achieving mTICI2b should be considered prudently for those with difficulty achieving 100% reperfusion.

Hybrid Palladium Catalyst Assembled from Chiral Phosphoric Acid and Thioamide for Enantioselective ß-C(sp3 )-H Arylation.

A hybrid palladium catalyst assembled from a chiral phosphoric acid (CPA) and thioamide enables a highly efficient and enantioselective ß-C(sp3 )-H functionalization of thioamides (up to 99 % yield, 97 % ee). A kinetic resolution of unsymmetrical thioamides by intermolecular C(sp3 )-H arylation can be achieved with high s-factors. Mechanistic investigations have revealed that stereocontrol is achieved by embedding the substrate in a robust chiral cavity defined by the bulky CPA and a neutral thioamide ligand.

The relationship between alkylamide compound content and pungency intensity of Zanthoxylum bungeanum based on sensory evaluation and ultra-performance liquid chromatography-mass spectrometry/ mass spectrometry (UPLC-MS/MS) analysis.

BACKGROUND: Zanthoxylum bungeanum originating in different places varies in alkylamide content and pungency intensity. RESULTS: The pungency intensity of 19 Zanthoxylum bungeanum samples was first determined with Scoville pungency units (SPUs). The SPUs were found to range from 3.80E + 04 to 5.40E + 05. The chemical compositions and contents were measured next, using the ultra-performance liquid chromatography-mass spectrometry/ mass spectrometry (UPLC-MS/MS) method. The total alkylamide content ranged from 9.83 ± 0.15 to 89.98 ± 1.35 g kg-1 . Hydroxy-ϵ-sanshool, hydroxy-α-sanshool, hydroxy-ß-sanshool, hydroxy-γ-sanshool, bungeanool, and isobungeanool were found to be the key pungent compounds, ranging in proportion from 92.65% to 97.69%. The relationship between alkymide compound content and pungency intensity was also analyzed by ridge regression, and it was found that the ß values of independent variables were stable when k was more than 0.6. The regression coefficients of hydroxy-ϵ-sanshool, hydroxy-α-sanshool, hydroxy-ß-sanshool, hydroxy-γ-sanshool, bungeanool, isobungeanool, and other alkylamides were 0.105, 0.177, 0.386, -0.166, -0.006, 0.005, and -0.018, respectively. CONCLUSION: Hydroxy- sanshool compounds were important in determinant the pungency intensity of Z. bungeanum. Knowledge of the relationship between alkymide compound content and pungency intensity will assist in the creation of new methods to determine pungency intensity and provide a scientific basis for flavor design, development of pungent food products, and consumer choice evaluations. © 2018 Society of Chemical Industry.

Assembling a Hybrid Pd Catalyst from a Chiral Anionic CoIII Complex and Ligand for Asymmetric C(sp3 )-H Functionalization.

An unusual hybrid palladium catalyst containing an anionic chiral CoIII complex and a chiral phosphoramidite ligand shows a high capacity for catalyzing asymmetric thioamide-directed C(sp3 )-H arylation and delivers excellent yield and enantioselectivity (up to 99 % yield, 99 % ee). Significant synergy between the chiral ligand and the anion in terms of stereochemical control was observed. Mechanistic investigations have revealed both the nature of the C-H activation and the origin of the enantioselectivity.

Prenatal phthalate exposure and placental size and shape at birth: A birth cohort study.

OBJECTIVE: There is concern over the potential placental effects of prenatal phthalate exposure, and the potential adverse effects of prenatal phthalate exposure require further study; however, few data are available in humans. We investigated the associations between phthalate exposure in each trimester and both placental size and shape at birth. METHODS: We measured the urinary concentrations of phthalate metabolites among 2725 pregnant women in the Ma'anshan Birth Cohort. Before collecting urine samples from each of the three trimesters, the pregnant women were interviewed via questionnaires. Placental information was obtained from hospital records. We estimated the sex-specific associations between urinary phthalate concentrations in each trimester and both placental size and shape at birth using adjusted multiple regression. A linear mixed model was used for the repeated measures analysis with subject-specific random intercepts and slopes for gestational age at sample collection to test the effect of phthalate levels on placental size and shape and to estimate the effect sizes. RESULTS: Overall, placental breadth increased by 0.148cm (95% CI: 0.078, 0.218) with each 1 ln-concentration increase in MBP in the first trimester. The difference between placental length and breadth (length-breadth) decreased by 0.086cm (95% CI: -0.159, -0.012) and 0.149cm (95% CI: -0.221, -0.076) with each 1 ln-concentration increase in MMP and MBP, respectively, in the first trimester. In the second trimester, placental thickness increased by 0.017cm (95% CI: 0.006, 0.027), 0.020cm (95% CI: 0.004, 0.036), 0.028cm (95% CI: 0.007, 0.048), and 0.035cm (95% CI: 0.018, 0.053) with each 1 ln-concentration increase in MMP, MBP, MEOHP, and MEHHP, respectively. In the third trimester, placental thickness increased by 0.037cm (95% CI: 0.019, 0.056) and 0.019cm (95% CI: 0, 0.037) with each 1 ln-concentration increase in MBP and MEHP, respectively. Multiple linear regression for each offspring sex indicated that prenatal phthalate exposure increased placental thickness in both the first and second trimesters in males, whereas the corresponding relationship was close to null in females. Linear mixed models (LMMs) yielded similar results. CONCLUSION: Our results suggest the presence of associations between prenatal phthalate exposure and placental size and shape. Exposure to certain phthalates may cause the placenta to become thicker and more circular. Associations appeared stronger for the subsample representing male offspring than those for the subsample representing female offspring. Given the few studies on this topic, additional research is warranted.

[Assessment of Left Atrial Appendage Size and Morphology by Enhanced Cardiac Computed Tomography in Patients with Non-valvular Atrial Fibrillation].

OBJECTIVE: This study was designed to investigate left atrial appendage (LAA) size and morphology characteristics in patients with non-valvular atrial fibrillation (NVAF) by enhanced cardiac computed tomography (CT) scanning,and to evaluate the predictive value of these parameters for thromboembolic risk. METHODS: A total of 189 NVAF patients were prospectively enrolled during December 2012 to January 2014 in West China Hospital of Sichuan University. Fifty-two atrial tachycardia patients without organ dysfunction were also recruited as controls. All subjects were scheduled for radiofrequency ablation and underwent enhanced cardiac CT scan. The clinical characteristics,comorbid diseases,anticoagulant therapy,and AF chronicity were collected and CHA2DS2-VASc score was calculated for the assessment of thromboembolic risk. The NVAF cohort was also divided further into LAA thrombus present (n=13) and absent (n=176) subgroup according to LAA with thrombus or not. Differencesin size and morphology characteristics of the LAA were compared among controls and different CHA2DS2-VASc thromboembolic risk subgroups,and between LAA thrombus and non-thrombus group. In addition,logistic regression analysis was used to identify whether these parameters predict thrombus formation independent of the CHA2DS2-VASc score in NVAF patients. RESULTS: Compared with controls,NVAF patients had significantly bigger orifice size. Windsock and cactus-type LAA were main morphology in controls,while the distribution of the four kinds of LAA types were similar in NVAF patients. The orifice and volume of the LAA were increased with increasing CHA2DS2-VASc riskscore,and chicken wing-type LAA was the predominant prevalence in low-intermediate thromboembolic risk subgroup while cauliflower in high thromboembolic risk subgroup. Compared with non-thrombus patients,LAA-thrombussubgroup exhibited a significantly increased orifice and volume,and higher prevalenceof the cauliflower shaped LAA. Logistic regression showed that the LAA orifice and cauliflower shape were independent predictors for thrombus formation in patients with NVAF following adjustment for the CHA2DS2-VASc score. CONCLUSION: Cardiac images obtained with CTis feasible for the analysis of LAA size and morphology,and these parameters provide incremental value in assessing the LAA thrombus risk in patients with NVAF.

[Effect of Qidan Granule on PMC Derived Peptide Content and Structure of Hippocampal CA1 Region in Microwave Radiated Rats].

OBJECTIVE: To explore the protection of high intensity microwave radiation on hypothalamo-pituitary-adrenal axis (HPAA) activity and hippocampal CA1 structure in rats and the protectiveeffect of Qindan Granule (QG) on radiation injured rats. METHODS: Totally 48 Wistar rats were randomlydivided into 8 groups, i.e., the normal control group, post-radiation day 1, 7, and 10 groups, 7 and 10days prevention groups, day 7 and 10 treatment groups, 6 in each group. Rats in prevention groups wererespectively administered with QG liquid (1 mL/100 g, 4. 75 g crude drugs) for 7 days and 10 days bygastrogavage and then microwave radiation. Then preventive effect for radiation injury was statisticallycalculated with the normal control group and the post-radiation day 1 group. Rats in treatment groupswere firstly irradiated, and then administered with QG liquid (1 mL/100 g, 4.75 g crude drugs). Finally preventive effect for radiation injury was statistically calculated with the normal control group, post-radiation day 7 and 10 groups. Contents of corticotrophin releasing hormone (CRH), beta endorphin (beta-EP), adrenocorticotropic hormone (ACTH), and heat shock protein 70 (HSP70) were detected. Morphological changes and structure of hippocampal CA1 region were observed under light microscope. RESULTS: Compared with the normal control group, contents of CRH and beta-EP significantly decreased in each radiation group. Serum contents of ACTH and beta-EP significantly increased in post-radiation day 1 and 7 groups (P < 0.05). Compared with radiation groups, beta-EP content in serum and pituitary significantly increased, and serum ACTH content significantly decreased in prevention groups (P < 0.05). Pituitary contents of CRH and beta-EP significantly increased in prevention groups. Serum contents of ACTH, beta-EP, and HSP70 were significantly lower in day 7 treatment group than post-radiation day 7 group (P < 0.05). Morphological results showed that pyramidal neurons in the hippocampal CA1 region arranged in disorder, with swollen cells, shrunken and condensed nucleus, dark dyeing cytoplasm, unclear structure. Vessels in partial regions were dilated with static blood; tissues were swollen and sparse. In prevention and treatment groups pathological damage of hippocampal CA1 region was obviously attenuated; neurons were arranged more regularly; swollen, pycnotic, or deleted neuron number were decreased; vascular dilatation and congestion was lessened. CONCLUSION: QG could affect HPAA function and activity of high intensity microwave radiated rats, showing certain preventive and therapeutic effects of microwave radiated rats by adjusting synthesis and release of partial bioactive peptides and hormones in HPAA, improving pathological injury in hippocampal CA1 region.

[Cloning and expression analysis of glucose-6-phosphate dehydrogenase 1 (G6PDH1) gene from Chimonanthus praecox].

Glucose-6-phosphate dehydrogenase is main regulatory enzyme for pentose phosphate pathway. To amplify the core sequence of G6PDH gene from Chimonanthus praecox, the primers were synthesized, based on the conserved nucleotide sequence of other reported plant G6PDH genes. The specific primers were designed according to the major fragment. The full length cDNA of the G6PDH1 gene was isolated by the 3' and 5' rapid amplification of cDNA ends approach. Transcript levels of G6PDH1 isoform was measured by real-time quantitative RT-PCR in different tissues and in responds to cold treatment. The G6PDH1 subcellular localization, transmembrane domain, three-dimensional structure, and phylogenetic analysis were predicted by different software to analysis the bioinformatics of G6PDH1 protein. The G6PDH1 cDNA sequence was 2 011 bp in length and consisted of 1 551 bp Open Reading Frame (ORF) , encoding a protein of 516 amino acids. Expression analysis results in different tissues showed that G6PDH1 was primarily observed in flowers and roots, as opposed to the leaves and stems. Cold treatment experiments indicated that cold treatment caused a rapid increase in G6PDH1 expression in flowers within 12 h. The full-length cDNA of G6PDH1 and its expression analysis will play an important role for further study on cold stress responses in Ch. praecox.

[Prevention of Inonotus obliquus polysaccharides for high power microwave radiation induced testicular injury in rats: an experimental research].

OBJECTIVE: To investigate the effect of Inonotus obliquus polysaccharides on testicular injury induced by exposure to high power microwave (HPM) in rats. METHODS: A total of 30 male Wistar rats were randomly divided into 5 groups, i.e., the normal control group, the microwave radiation model group, the treatment group, the new microwave radiation model group, and the prevention group, 6 in each group. All rats, except those in the normal control group, were exposed to microwave at an average power density of 200 mW/cm2 for 6 min. Rats in the control group and the model group were administered with normal saline by gastrogavage, once a day. Rats in the treatment group and the prevention group were given with Inonotus obliquus polysaccharides by gastrogavage, 2 mL each time (400 mg/kg body weight), once a day. All rats were sacrificed on the 11th day.The sperm density and the rate of sperm deformity were determined. Pathological changes of testis were observed by light microscope and transmission electron microscope. RESULTS: Short-term HPM irradiation could significantly reduce the sperm density and increase the sperm deformity rate (P < 0.05). Meanwhile, obvious pathological changes of testes occurred. Compared with the two model groups, the sperm density increased and the sperm deformity rate decreased in the treatment group and the prevention group (P < 0.05). Under the light microscope, injuries of spermatogenic cells and stromal cells, as well as vascular dilatation and congestion were obviously alleviated in the treatment group and the prevention group. Mitochondrial swelling and endoplasmic reticulum expansion shown by ultrastructural observation were also significantly alleviated. Of them, injuries of spermatogenic cells and inflammation response were milder in the treatment group than in the prevention group. CONCLUSIONS: Inonotus obliquus polysaccharides had significant protective effect on microwave radiation induced testicular injury. Better effect was obtained by therapeutic medication than preventive medication.