Arabidopsis AGAMOUS-LIKE16 and SUPPRESSOR OF CONSTANS1 regulate the genome-wide expression and flowering time.

Flowering transition is tightly coordinated by complex gene regulatory networks, in which AGAMOUS-LIKE 16 (AGL16) plays important roles. Here, we identified the molecular function and binding properties of AGL16 and demonstrated its partial dependency on the SUPPRESSOR OF CONSTANS 1 (SOC1) function in regulating flowering. AGL16 bound to promoters of more than 2,000 genes via CArG-box motifs with high similarity to that of SOC1 in Arabidopsis (Arabidopsis thaliana). Approximately 70 flowering genes involved in multiple pathways were potential targets of AGL16. AGL16 formed a protein complex with SOC1 and shared a common set of targets. Intriguingly, only a limited number of genes were differentially expressed in the agl16-1 loss-of-function mutant. However, in the soc1-2 knockout background, AGL16 repressed and activated the expression of 375 and 182 genes, respectively, with more than a quarter bound by AGL16. Corroborating these findings, AGL16 repressed the flowering time more strongly in soc1-2 than in the Col-0 background. These data identify a partial inter-dependency between AGL16 and SOC1 in regulating genome-wide gene expression and flowering time, while AGL16 provides a feedback regulation on SOC1 expression. Our study sheds light on the complex background dependency of AGL16 in flowering regulation, thus providing additional insights into the molecular coordination of development and environmental adaptation.

Transformation to small cell lung cancer is irrespective of EGFR and accelerated by SMAD4-mediated ASCL1 transcription independently of RB1 in non-small cell lung cancer.

OBJECTIVES: Histological transformation to small cell lung cancer (SCLC) has been identified as a mechanism of TKIs resistance in EGFR-mutant non-small cell lung cancer (NSCLC). We aim to explore the prevalence of transformation in EGFR-wildtype NSCLC and the mechanism of SCLC transformation, which are rarely understood. METHODS: We reviewed 1474 NSCLC patients to investigate the NSCLC-to-SCLC transformed cases and the basic clinical characteristics, driver gene status and disease course of them. To explore the potential functional genes in SCLC transformation, we obtained pre- and post-transformation specimens and subjected them to a multigene NGS panel involving 416 cancer-related genes. To validate the putative gene function, we established knocked-out models by CRISPR-Cas 9 in HCC827 and A549-TP53-/- cells and investigated the effects on tumor growth, drug sensitivity and neuroendocrine phenotype in vitro and in vivo. We also detected the expression level of protein and mRNA to explore the molecular mechanism involved. RESULTS: We firstly reported an incidence rate of 9.73% (11/113) of SCLC transformation in EGFR-wildtype NSCLC and demonstrated that SCLC transformation is irrespective of EGFR mutation status (P = 0.16). We sequenced 8 paired tumors and identified a series of mutant genes specially in transformed SCLC such as SMAD4, RICTOR and RET. We firstly demonstrated that SMAD4 deficiency can accelerate SCLC transition by inducing neuroendocrine phenotype regardless of RB1 status in TP53-deficient NSCLC cells. Further mechanical experiments identified the SMAD4 can regulate ASCL1 transcription competitively with Myc in NSCLC cells and Myc inhibitor acts as a potential subsequent treatment agent. CONCLUSIONS: Transformation to SCLC is irrespective of EFGR status and can be accelerated by SMAD4 in non-small cell lung cancer. Myc inhibitor acts as a potential therapeutic drug for SMAD4-mediated resistant lung cancer. Video Abstract.

Silver(I) Complexes with Mefenamic Acid and Nitrogen Heterocyclic Ligands: Synthesis, Characterization, and Biological Evaluation.

Four Ag(I) complexes with mefenamato and nitrogen heterocyclic ligands, [Ag(2-apy)(mef)]2 (1), [Ag(3-apy)(mef)] (2), [Ag2(tmpyz)(mef)2] (3), and {[Ag(4,4'-bipy)(mef)]2(CH3CN)1.5(H2O)2}n (4), (mef = mefenamato, 2-apy = 2-aminopyridine, 3-apy = 3-aminopyridine, tmpyz = 2,3,5,6-tetramethylpyrazine, 4,4'-bipy = 4,4'-bipyridine), were synthesized and characterized. The interactions of these complexes with BSA were investigated by fluorescence spectroscopy, which indicated that these complexes quench the fluorescence of BSA by a static mechanism. The fluorescence data also indicated that the complexes showed good affinity for BSA, and one binding site on BSA was suitable for the complexes. The in vitro cytotoxicity of the four complexes against human cancer cell lines (MCF-7, HepG-2, A549, and MDA-MB-468) and one normal cell line (HTR-8) was evaluated by the MTT assay. Complex 1 displayed high cytotoxic activity against A549 cells. Further studies revealed that complex 1 could enhance the intracellular levels of ROS (reactive oxygen species) in A549 cells, cause cell cycle arrest in the G0/G1 phase, and induce apoptosis in A549 cells in a dose-dependent manner.

Metabolome and Genome Analysis of a Novel Endophytic Fungus Aureobasidium pullulans KB3: Discovery of Polyketones and Polyketone Biosynthesis Pathway.

Endophytic fungi associated with plants may contain undiscovered bioactive compounds. Under standard laboratory conditions, most undiscovered compounds are inactive, whereas their production could be stimulated under different cultivation conditions. In this study, six endophytic fungi were isolated from the bark of Koelreuteria paniculata in Quancheng Park, Jinan City, Shandong Province, one of which was identified as a new subspecies of Aureobasidium pullulans, named A. pullulans KB3. Additionally, metabolomic tools were used to screen suitable media for A. pullulans KB3 fermentation, and the results showed that peptone dextrose medium (PDM) was more beneficial to culture A. pullulans KB3 for isolation of novel compounds. Sphaerolone, a polyketone compound, was initially isolated from A. pullulans KB3 via scaled up fermentation utilizing PDM. Additionally, the whole-genome DNA of A. pullulans KB3 was sequenced to facilitate compound isolation and identify the biosynthesis gene clusters (BGCs). This study reports the multi-omics (metabolome and genome) analysis of A. pullulans KB3, laying the foundation for discovering novel compounds of silent BGCs and identifying their biosynthesis pathway.

(S)-N-Benzyl-1-phenyl-3,4-dihydroisoqunoline-2(1H)-carboxamide Derivatives, Multi-Target Inhibitors of Monoamine Oxidase and Cholinesterase: Design, Synthesis, and Biological Activity.

A series of (S)-1-phenyl-3,4-dihydroisoquinoline-2(1H)-carboxamide derivatives was synthesized and evaluated for inhibitory activity against monoamine oxidase (MAO)-A and-B, acetylcholine esterase (AChE), and butyrylcholine esterase (BChE). Four compounds (2i, 2p, 2t, and 2v) showed good inhibitory activity against both MAO-A and MAO-B, and two compounds (2d and 2j) showed selective inhibitory activity against MAO-A, with IC50 values of 1.38 and 2.48 µM, respectively. None of the compounds showed inhibitory activity against AChE; however, 12 compounds showed inhibitory activity against BChE. None of the active compounds showed cytotoxicity against L929cells. Molecular docking revealed several important interactions between the active analogs and amino acid residues of the protein receptors. This research paves the way for further study aimed at designing MAO and ChE inhibitors for the treatment of depression and neurodegenerative disorders.

Cinnamaldehyde prevents intergenerational effect of paternal depression in mice via regulating GR/miR-190b/BDNF pathway.

Paternal stress exposure-induced high corticosterone (CORT) levels may contribute to depression in offspring. Clinical studies disclose the association of depressive symptoms in fathers with their adolescent offspring. However, there is limited information regarding the intervention for intergenerational inheritance of depression. In this study we evaluated the intervention of cinnamaldehyde, a major constituent of Chinese herb cinnamon bark, for intergenerational inheritance of depression in CORT- and CMS-induced mouse models of depression. Depressive-like behaviors were induced in male mice by injection of CORT (20 mg·kg-1·d-1, sc) for 6 weeks or by chronic mild stress (CMS) for 6 weeks. We showed that co-administration of cinnamaldehyde (10, 20, or 40 mg·kg-1·d-1, ig) for 6 weeks in F0 males prevented the depressive-like phenotypes of F1 male offspring. In addition, co-administration of cinnamaldehyde (20 mg·kg-1·d-1, ig) for 4 weeks significantly ameliorated depressive-like behaviors of chronic variable stress (CVS)-stimulated F1 offspring born to CMS mice. Notably, cinnamaldehyde had no reproductive toxicity, while positive drug fluoxetine showed remarkable reproductive toxicity. We revealed that CMS and CORT significantly reduced testis glucocorticoid receptor (GR) expression, and increased testis and sperm miR-190b expression in F0 depressive-like models. Moreover, pre-miR-190b expression was upregulated in testis of F0 males. The amount of GR on miR-190b promoter regions was decreased in testis of CORT-stimulated F0 males. Cinnamaldehyde administration reversed CORT-induced GR reduction in testis, miR-190b upregulation in testis and sperm, pre-miR-190b upregulation in testis, and the amount of GR on miR-190b promoter regions of F0 males. In miR-190b-transfected Neuro 2a (N2a) cells, we demonstrated that miR-190b might directly bind to the 3'-UTR of brain-derived neurotrophic factor (BDNF). In the hippocampus of F1 males of CORT- or CMS-induced depressive-like models, increased miR-190b expression was accompanied by reduced BDNF and GR, which were ameliorated by cinnamaldehyde. In conclusion, cinnamaldehyde is a potential intervening agent for intergenerational inheritance of depression, probably by regulating GR/miR-190b/BDNF pathway.

Development and validation of a nomogram to predict survival for advanced male breast cancer.

Male breast cancer is a rare disease. Many experiences of male breast cancer were derived of female breast cancer. However, there are huge differences between two groups. We conducted this study to find a reliable prognostic model for advanced male breast cancer. The cohort was selected from the Surveillance, Epidemiology, and End Results database. The enrolled patients were randomly divided into training and validation group. The univariate and multivariate analyses were used for prognostic assessment and a nomogram was built. Calibration curves and concordance index were compiled to determine predictive and discriminatory capacity. The time-dependent receiver operating curves and the decision curve analysis was used to verify the model's ability. Two hundred and eighty individuals were enrolled. The cumulative rates of 1-, 3- and 5-year overall survival (OS) rates were 98.6%, 72% and 57.9%. The C-indexes for OS were 0.835 (95%CI, 0.777-0.893) in the training group and 0.765 (95%CI, 0.668-0.862) in the validation group. The calibration curves confirmed the consistency of the nomogram both in the training and validation group. The time-dependent receiver operating curves and decision curve analysis demonstrated that the nomogram had better prediction capacity than TNM stage system for advanced male breast cancer. The nomogram we built was a reliable and solid predictive model.

[Multicenter, Randomized, Double-Blind, and Positive Drug-Controlled Clinical Trial on Prevention of Postpartum Hemorrhage after Vaginal Delivery with Ergometrine Maleate].

Objective: To evaluate the safety and efficacy of using ergometrine maleate injection combined with oxytocin injection, with oxytocin injection as the control, to prevent postpartum hemorrhage after vaginal delivery. Methods: A total of 305 cases who underwent vaginal delivery between December 2018 and November 2019 in 16 hospitals across China were enrolled and included in the full analysis set (FAS) and the safety analysis set (SS). Among the 299 subjects who completed the trial, 277 were included in the per protocol set (PPS). The subjects were randomly assigned by 1∶1 ratio to two groups, 152 cases in Group A, the experimental group receiving oxytocin injection plus ergometrine injection, and 153 cases in Group B, the control group, receiving oxytocin injection. The difference in total bleeding volume at 2 h, 6 h and 24 h postpartum in the two groups was documented and compared. Other measures were also compared between the two groups, including the proportion of additional use of uterotonics and hemostatic drugs or other hemostatic measures 2 h and 24 h postpartum, the proportion of subjects needing blood transfusion, the time of placenta retention, proportion of subjects with prolonged hospital stay due to uterine asthenia, the vital signs, lab test indicators and the incidence of adverse reactions in the two groups. Results: The total bleeding volume at 2 h, 6 h and 24 h after delivery was significantly lower in the experimental group (P<0.05). There was no significant difference between the two groups in the proportion of additional use of uterotonics and hemostatic drugs or other hemostatic measures 2 h and 24 h postpartum, the proportion of subjects needing blood transfusion and the time of placenta retention, heart rate, respiration, lab test indicators, or the incidence of adverse reaction (P>0.05). Conclusion: Ergometrine maleate injection showed evident therapeutic efficacy in preventing hemorrhage after vaginal delivery, causing fewer adverse reactions and ensuring greater safety, and therefore, presenting promising prospects for clinical application.

Comprehensive analysis of formin gene family highlights candidate genes related to pollen cytoskeleton and male fertility in wheat (Triticum aestivum L.).

BACKGROUND: Formin, a highly conserved multi-domain protein, interacts with microfilaments and microtubules. Although specifically expressed formin genes in anthers are potentially significant in research on male sterility and hybrid wheat breeding, similar reports in wheat, especially in thermo-sensitive genic male sterile (TGMS) wheat, remain elusive. RESULTS: Herein, we systematically characterized the formin genes in TGMS wheat line BS366 named TaFormins (TaFHs) and predicted their functions in inducing stress response. In total, 25 TaFH genes were uncovered, majorly localized in 2A, 2B, and 2D chromosomes. According to the neighbor-joining (NJ) method, all TaFH proteins from wheat and other plants clustered in 6 sub-groups (A-F). The modeled 3D structures of TaFH1-A/B, TaFH2-A/B, TaFH3-A/B and TaFH3-B/D were validated. And different numbers of stress and hormone-responsive regulatory elements in their 1500 base pair promoter regions were contained in the TaFH genes copies. TaFHs had specific temporal and spatial expression characteristics, whereby TaFH1, TaFH4, and TaFH5 were expressed highly in the stamen of BS366. Besides, the accumulation of TaFHs was remarkably lower in a low-temperature sterile condition (Nanyang) than fertile condition (Beijing), particularly at the early stamen development stage. The pollen cytoskeleton of BS366 was abnormal in the three stages under sterile and fertile environments. Furthermore, under different stress levels, TaFHs expression could be induced by drought, salt, abscisic acid (ABA), salicylic acid (SA), methyl jasmonate (MeJA), indole-3-acetic acid (IAA), polyethylene glycol (PEG), and low temperature. Some miRNAs, including miR167, miR1120, and miR172, interacts with TaFH genes; thus, we constructed an interaction network between microRNAs, TaFHs, phytohormone responses, and distribution of cytoskeleton to reveal the regulatory association between upstream genes of TaFH family members and sterile. CONCLUSIONS: Collectively, this comprehensive analysis provides novel insights into TaFHs and miRNA resources for wheat breeding. These findings are, therefore, valuable in understanding the mechanism of TGMS fertility conversion in wheat.

Genome-wide identification and transcriptional characterization of DNA methyltransferases conferring temperature-sensitive male sterility in wheat.

BACKGROUND: DNA methyltransferase (DMT) genes contribute to plant stress responses and development by de novo establishment and subsequent maintenance of DNA methylation during replication. The photoperiod and/or temperature-sensitive genic male sterile (P/TGMS) lines play an important role in hybrid seed production of wheat. However, only a few studies have reported on the effect of DMT genes on temperature-sensitive male sterility of wheat. Although DMT genes have been investigated in some plant species, the identification and analysis of DMT genes in wheat (Triticum aestivum L.) based on genome-wide levels have not been reported. RESULTS: In this study, a detailed overview of phylogeny of 52 wheat DMT (TaDMT) genes was presented. Homoeolog retention for TaDMT genes was significantly above the average retention rate for whole-wheat genes, indicating the functional importance of many DMT homoeologs. We found that the strikingly high number of TaDMT genes resulted mainly from the significant expansion of the TaDRM subfamily. Intriguingly, all 5 paralogs belonged to the wheat DRM subfamily, and we speculated that tandem duplications might play a crucial role in the TaDRM subfamily expansion. Through the transcriptional analysis of TaDMT genes in a TGMS line BS366 and its hybrids with the other six fertile lines under sterile and fertile conditions, we concluded that TaCMT-D2, TaMET1-B1, and TaDRM-U6 might be involved in male sterility in BS366. Furthermore, a correlation analysis showed that TaMET1-B1 might negatively regulate the expression of TaRAFTIN1A, an important gene for pollen development, so we speculated regarding an epigenetic regulatory mechanism underlying the male sterility of BS366 via the interaction between TaMET1-B1 and TaRAFTIN1A. CONCLUSIONS: Our findings presented a detailed phylogenic overview of the DMT genes and could provide novel insights into the effects of DMT genes on TGMS wheat.

Impact of glycemic control on the association of endothelial dysfunction and coronary artery disease in patients with type 2 diabetes mellitus.

BACKGROUND: We investigated whether glycemic control affects the relation between endothelial dysfunction and coronary artery disease in patients with type 2 diabetes mellitus (T2DM). METHODS: In 102 type 2 diabetic patients with stable angina, endothelial function was evaluated using brachial artery flow-mediated dilation (FMD) with high-resolution ultrasound, and significant stenosis of major epicardial coronary arteries (≥ 50% diameter narrowing) and degree of coronary atherosclerosis (Gensini score and SYNTAX score) were determined. The status of glycemic control was assessed by blood concentration of glycated hemoglobin (HbA1c). RESULTS: The prevalence of significant coronary artery stenosis (67.9% vs. 37.0%, P = 0.002) and degree of coronary atherosclerosis (Gensini score: 48.99 ± 48.88 vs. 15.07 ± 21.03, P < 0.001; SYNTAX score: 15.88 ± 16.36 vs. 7.28 ± 10.54, P = 0.003) were higher and FMD was lower (6.03 ± 2.08% vs. 6.94 ± 2.20%, P = 0.036) in diabetic patients with poor glycemic control (HbA1c ≥ 7.0%; n = 56) compared to those with good glycemic control (HbA1c < 7.0%; n = 46). Multivariate regression analysis revealed that tertile of FMD was an independent determinant of presence of significant coronary artery stenosis (OR = 0.227 95% CI 0.056-0.915, P = 0.037), Gensini score (ß = - 0.470, P < 0.001) and SYNTAX score (ß = - 0.349, P = 0.004) in diabetic patients with poor glycemic control but not for those with good glycemic control (P > 0.05). CONCLUSION: Poor glycemic control negatively influences the association of endothelial dysfunction and coronary artery disease in T2DM patients.

Apilactobacillus nanyangensis sp. nov., Secundilactobacillus hailunensis sp. nov., Secundilactobacillus yichangensis sp. nov., Levilactobacillus andaensis sp. nov., Levilactobacillus wangkuiensis sp. nov., Levilactobacillus lanxiensis sp. nov., Lacticaseibacillus mingshuiensis sp. nov. and Lacticaseibacillus suilingensis sp. nov., isolated from traditional Chinese pickle and the gut of honeybee (Apis mellifera).

Thirteen Gram-stain-positive bacterial strains were isolated from Chinese traditional pickle and the gut of honeybee (Apis mellifera). These strains were characterized using a polyphasic taxonomic approach. The data demonstrated that 12 of the 13 strains represented eight novel species belonging to the genera Apilactobacillus, Secundilactobacillus, Levilactobacillus and Lacticaseibacillus; strains HN36-1T, 887-11T, F79-211-2T, 866-3T, 6-5(1)T, 13B17T, 117-1T and ZW152T were designated as the type strains. Based upon the data of polyphasic characterization obtained in the present study, eight novel species, Apilactobacillus nanyangensis sp. nov., Secundilactobacillus hailunensis sp. nov., Secundilactobacillus yichangensis sp. nov., Levilactobacillus andaensis sp. nov., Levilactobacillus wangkuiensis sp. nov., Levilactobacillus lanxiensis sp. nov., Lacticaseibacillus mingshuiensis sp. nov. and Lacticaseibacillus suilingensis sp. nov., are proposed and the type strains are HN36-1T (=JCM 33867T=CCTCC AB 2019385T), 887-11T (=NCIMB 15201T=CCM 8950T=JCM 33864T=CCTCC AB 2018396T), F79-211-2T (=NCIMB 15254T=JCM 33866T=CCTCC AB 2019384T), 866-3T (=JCM 33863T=CCTCC AB 2019383T), 6-5(1)T (=NCIMB 15229T=CCM 8977T=JCM 33564T=CCTCC AB 2019168T), 13B17T (=NCIMB 15230T=CCM 8979T=JCM 33565T=CCTCC AB 2019167T), 117-1T (=NCIMB 15232T=CCM 8980T=JCM 33567T) and ZW152T (=JCM 34363T=CCTCC AB 2020299T=LMG 32143T=CCM 9110T), respectively.

Evaluation of fecal microbiota transplantation in Parkinson's disease patients with constipation.

Parkinson's disease (PD) is a neurodegenerative disorder and 70-80% of PD patients suffer from gastrointestinal dysfunction such as constipation. We aimed to assess the efficacy and safety of fecal microbiota transplantation (FMT) for treating PD related to gastrointestinal dysfunction. We conducted a prospective, single- study. Eleven patients with PD received FMT. Fecal samples were collected before and after FMT and subjected to 16S ribosomal DNA (rDNA) gene sequencing. Hoehn-Yahr (H-Y) grade, Unified Parkinson's Disease Rating Scale (UPDRS) score, and the Non-Motion Symptom Questionnaire (NMSS) were used to assess improvements in motor and non-motor symptoms. PAC-QOL score and Wexner constipation score were used to assess the patient's constipation symptoms. All patients were tested by the small intestine breath hydrogen test, performed before and after FMT. Community richness (chao) and microbial structure in before-FMT PD patients were significantly different from the after-FMT. We observed an increased abundance of Blautia and Prevotella in PD patients after FMT, while the abundance of Bacteroidetes decreased dramatically. After FMT, the H-Y grade, UPDRS, and NMSS of PD patients decreased significantly. Through the lactulose H2 breath test, the intestinal bacterial overgrowth (SIBO) in PD patients returned to normal. The PAC-QOL score and Wexner constipation score in after-FMT patients decreased significantly. Our study profiles specific characteristics and microbial dysbiosis in the gut of PD patients. FMT might be a therapeutic potential for reconstructing the gut microbiota of PD patients and improving their motor and non-motor symptoms.

Prediction of in-hospital mortality in status epilepticus: Evaluation of four scoring tools in younger and older adult patients.

OBJECTIVE: The goal of this study was to evaluate the predictive capacity of four scoring tools: the Status Epilepticus Severity Score (STESS), the Encephalitis-NCSE-Diazepam resistance-Image abnormalities-Tracheal intubation (END-IT) score, and two variable combinations of the Epidemiology-based Mortality Score in Status Epilepticus (EMSE) in younger and older adult patients with status epilepticus (SE). METHODS: We present a retrospective hospital-based analysis with a focus on adult patients with SE at three tertiary care hospitals in the Zhejiang province of China. Data were collected from January 2013 to December 2018. The patients were divided into two groups: younger adult patients (18-64 years old) and older adult patients (≥65 years old). Clinical outcomes (dead or alive) were assessed at hospital discharge. The four scoring tools were used to predict in-hospital mortality in both younger and older adult patients. RESULTS: The mortality rate in older adult patients (25.4%) was higher than in younger adult patients (12.9%). Compared with the elderly, the younger adult patients had a higher proportion of encephalitis, while acute cerebrovascular disease and Charlson Complications Index (CCI) were lower. For the younger adult patients, END-IT had the largest area under the curve (AUC) of 0.843 (95% CI, 0.772-0.899), which was higher than the EMSE-EAL value of 0.687 (95% CI, 0.603-0.763, p < 0.05) and EMSE-EAC of 0.646 (95% CI, 0.561-0.725, p < 0.05). For the older adult patients, EMSE-EAL had the largest AUC of 0.843 (95% CI, 0.738-0.919), which was significantly higher than STESS with an AUC of 0.676 (95% CI, 0.554-0.782, p < 0.05). Moreover, the AUC of EMSE-EAL in the elderly was larger than in younger adult patients. The cutoffs in younger adult patients were STESS ≥ 4 (sensitivity 0.444, specificity 0.951), END-IT ≥ 3 (sensitivity 0.833, specificity 0.672), EMSE-EAL ≥ 31 (sensitivity 0.778, specificity 0.566), and EMSE-EAC ≥ 33 (sensitivity 0.833, specificity 0.492). However, the cutoffs in older adult patients were STESS ≥ 5 (sensitivity 0.500, specificity 0.925), END-IT ≥ 2 (sensitivity 0.944, specificity 0.547), EMSE-EAL ≥ 30 (sensitivity 0.944, specificity 0.623), and EMSE-EAC ≥ 31 (sensitivity 0.944, specificity 0.415). CONCLUSION: Our results indicated that the STESS, END-IT, EMSE-EAC, and EMSE-EAL scores have excellent capacity to predict in-hospital mortality in both younger and older adult patients with SE. Our study supports the use of END-IT in patients under 65 years of age and suggests that EMSE-EAL is the most suitable scoring tool for patients over 65.

Using circulating O-sulfotyrosine in the differential diagnosis of acute kidney injury and chronic kidney disease.

BACKGROUND: Sulfation of tyrosine, yielding O-sulfotyrosine, is a common but fixed post-translational modification in eukaryotes. Patients with increased circulating O-sulfotyrosine levels experience a faster decline in renal function with progression to end-stage renal disease (ESRD). In the present study, we measured serum O-sulfotyrosine levels in individuals with chronic kidney disease (CKD) and acute kidney injury (AKI) to explore its ability to differentiate AKI from CKD. METHODS: A total of 135 patients (20 with AKI and 115 with CKD) were recruited prospectively for liquid chromatography-mass spectrometry assessment of circulating O-sulfotyrosine. We also studied C57BL/6 mice with CKD after 5/6 nephrectomy (Nx). Blood samples were drawn from the tail vein on Day 1, 3, 5, 7, 14, 30, 60, and 90 after CKD. Serum separation and characterization of creatinine, blood urea nitrogen (BUN), and O-sulfotyrosine was performed. Thus, the time-concentration curves of the O-sulfotyrosine level demonstrate the variation of kidney dysfunction. RESULTS: The serum levels of O-sulfotyrosine were markedly increased in patients with CKD compared with AKI. Median O-sulfotyrosine levels in CKD patients versus AKI, respectively, were as follows:243.61 ng/mL(interquartile range [IQR] = 171.90-553.86) versus 126.55 ng/mL (IQR = 48.19-185.03, P = 0.004). In patients with CKD, O-sulfotyrosine levels were positively correlated with creatinine, BUN, and Cystatin C (r = 0.63, P < 0.001; r = 0.49, P < 0.001; r = 0.61, P < 0.001, respectively) by the multivariate linear regression analysis (ß = 0.71, P < 0.001; ß = 0.40, P = 0.002; ß = 0.73, P < 0.001, respectively). However, this association was not statistically significant in patients with AKI (r = - 0.17, P = 0.472; r = 0.11, P = 0.655; r = 0.09, P = 0.716, respectively). The receiver operating characteristic (ROC) analysis illustrated that the area under the curve was 0.80 (95% confidence interval [CI] 0.71-0.89; P < 0.001) and the optimal cut-off value of serum O-sulfotyrosine suggesting AKI was < 147.40 ng/mL with a sensitivity and specificity of 80.90 and 70.00% respectively. In animal experiments, serum levels of O-sulfotyrosine in mice were elevated on Day 7 after 5/6 nephrectomy (14.89 ± 1.05 vs. 8.88 ± 2.62 ng/mL, P < 0.001) until Day 90 (32.65 ± 5.59 vs. 8.88 ± 2.62 ng/mL, P < 0.001). CONCLUSION: Serum O-sulfotyrosine levels were observed correlated with degrading renal function and in CKD patients substantially higher than those in AKI patients. Thus serum O-sulfotyrosine facilitated the differential diagnosis of AKI from CKD.

Unveiling Catalytic Sites in a Typical Hydrogen Photogeneration System Consisting of Semiconductor Quantum Dots and 3d-Metal Ions.

Semiconductor quantum dots (QDs) in conjunction with non-noble 3d-metal ions (e.g., Fe3+, Co2+, and Ni2+) have emerged as an extremely efficient, facile, and cost-effective means of solar-driven hydrogen (H2) evolution. However, the exact structural change of the active sites under realistic conditions remains elusive, and the mechanism of H2 evolution behind the remarkable activity is poorly understood. Here, we successfully track the structural variation of the catalytic sites in the typical H2 photogeneration system consisting of CdSe/CdS QDs and 3d-metal ions (i.e., Ni2+ used here). That is, the nickel precursor of Ni(OAc)2 changes to Ni(H2O)62+ in neutral H2O and eventually transforms to Ni(OH)2 nanosheets in alkaline media. Furthermore, the in operando spectroscopic techniques of electron paramagnetic resonance and X-ray absorption spectroscopy reveal the photoinduced transformation of Ni(OH)2 to a defective structure [Nix0/Ni1-x(OH)2], which acts as the real catalytic species of H2 photogeneration. Density functional theory (DFT) calculations further indicate that the surface Ni-vacancies (VNi) on the Ni(OH)2 nanosheets enhance the adsorption and dissociation of H2O molecules to enhance the local proton concentration, while the Ni0 clusters behave as H2-evolution sites, thereby synergistically promoting the activity of H2 photogeneration in alkaline media.

Preparation, characterization, and application of soluble liquid crystalline molecularly imprinted polymer in electrochemical sensor.

A novel soluble molecularly imprinted polymer (SMIP) without chemical cross-linker was successfully synthesized. The quinine (QN), which the structure was similar to the template, was chosen as the immobile template to improve the affinity of MIP. 4-Methyl phenyl dicyclohexyl ethylene (MPDE) was used as the liquid crystal (LC) monomer to increase the rigid of the composite. The cooperative effect of QN and MPDE was demonstrated by comparing with the conventional MIP, which synthesized without QN and MPDE. The polymerization conditions of SMIP including the ratio of MAA to MPDE, template to functional monomer, and HQN to QN were also optimized. Moreover, the characterizations of the SMIP were investigated by the transmission electron microscopy (TEM), field emission scanning electron microscopy (SEM), thermogravimetric analysis (TGA), X-ray diffraction (XRD), and nitrogen adsorption. In binding behavior, the SMIP presented the maximum adsorption capacity (0.37 ± 0.06 mmol/g) and imprinting factor (3.44 ± 0.25). And above all, the obtained polymer exhibited the solubility in the organic solution. In addition, the proposed SMIP as the electrochemical sensor exhibited a significant conductivity and sensitivity with the detection limit of 0.33 µM for HQN, the recoveries for the sample analysis varied from 97.4 to 100.8%, and the intra-day precision and inter-day precision were within 5.5% and 12.5%, respectively. It turned out that the SMIP had demonstrated more excellent potential than the traditional insoluble MIP in the development of the membrane-based electrochemical sensors.Graphical abstract.

Improving the ability to predict hospital mortality among adults by combining two status epilepticus outcome scoring tools.

OBJECTIVE: The goal of this study was to compare the predictive ability of the Status Epilepticus Severity Score (STESS), the Encephalitis-nonconvulsive status epilepticus (NCSE)-Diazepam resistance-Image abnormalities-Tracheal intubation (END-IT), and the combination of these two scoring tools to predict mortality among inhospital patients with status epilepticus (SE). METHODS: A retrospective analysis was conducted of adult patients with SE who were admitted to the neurology department, the emergency department, and the intensive care unit from January 2013 to December 2017. The patients were divided into two groups: survivors and nonsurvivors. The STESS data were obtained when the patient arrived at the hospital, and the END-IT data were collected 24 h after patients were initially treated in the hospital. The ability of the scoring tools to predict death in patients with SE, alone or in combination, was evaluated. RESULTS: A total of 123 patients with SE were included in the study, of which 22 died, for a mortality rate of 17.9%. The STESS and END-IT scores of nonsurvivors were both significantly higher than those of survivors (median STESS 4 vs. 2, p = 0.003; median END-IT 3 vs. 1, p < 0.001). The area under the receiver operating characteristic curve (AUC) was 0.698 for the STESS and 0.852 for the END-IT, and the cutoff values were 4 and 3, respectively. The AUC of the END-IT with the optimal cutoff value was larger than that of the STESS (p = 0.024). The sensitivity and specificity of combining the STESS and END-IT by the serial method (STESS ≥ 4∩END-IT ≥ 3) were 0.50 and 0.95, respectively, and the specificity was significantly higher than the STESS or END-IT (both p's < 0.001). The sensitivity and specificity of combining the STESS and END-IT by the parallel method (STESS ≥ 4⋃END-IT ≥ 3) were 0.91 and 0.53, respectively, and the sensitivity was higher than the STESS was (p = 0.016). CONCLUSION: Our results indicated that the combined score of the STESS and END-IT systems was a better predictor of survival of patients with SE than the scores of either the STESS system or the END-IT system alone and that combining the scores may be considered to be a new method for early identification of patients for both good and bad outcomes.

Influence of the arrangement of vacuum chuck holes on the transmittance wavefront of large-aperture KDP in single-point diamond turning.

Serious edge effects of potassium dihydrogen phosphate (${{\rm KH}_2}{{\rm PO}_4}$KH2PO4, KDP) manufactured using single-point diamond turning (SPDT) often result in disqualification of the transmittance wavefront for high-power laser systems. In this paper, based on the theoretical analysis of sucker hole configuration and the pressure distribution law under the vacuum chuck condition of crystal elements, the influence of sucker hole configuration on the transmittance wavefront root-mean-square gradient (GRMS) is verified through fly-cutting experiments. By adopting the newly designed vacuum chuck, the vacuum-chucking quality is effectively improved, and the edge effect is accordingly suppressed in the SPDT. Moreover, the accuracy of the transmittance wavefront GRMS has an improvement of about 25% under the same processing parameters.