hROS-Responsive Behavior for Long-Term Stability of Cellulosic Gold Nanoclusters.

Understanding the gold core-ligand interaction in gold nanoclusters (GNCs) is essential for the on-demand tailoring of their photoluminescence properties and long-term stability. Here, inspired by the suckers arranged directionally on the tentacles of octopus, a series of GNCs with regulating ligand structures are grown and stabilized on the cellulose nanocrystals (CNCs). The carboxylated CNCs providing an electron-rich environment to promote the luminescence of GNCs and stabilize it within a long-term of 1 year through anchoring and diluting effects, and the highest quantum yields reaches 31.02% in ultrapure water. Interestingly, this bionic preparation strategy is generally applicable to various ligands for tailoring on-demand hROS-responsive and nonresponsive GNCs to construct tunable-emission wavelength dual GNCs ratiometric probes. The results show that designing a specific ligand structure to inhibit the transformation of Au-Au to Au (I)-ligand in GNCs is crucial to regulate the hROS-responsive characteristics. As expected, the interfacial compatible dual GNCs ratiometric probe with a hROS limit of detection of 0.74 µmol L-1 can diagnose certain diseases through intracellular hROS imaging. This work provides important insights for understanding the gold core-ligand interaction in GNCs during the oxidation process triggered by intracellular hROS.

Magnetic-field-assisted optical fiber quantum temperature sensor with enhanced sensitivity.

In recent years, utilizing nitrogen-vacancy color centers in diamond for temperature sensing has drawn great attention. However, increasing the sensitivity has encountered challenges due to the intrinsic temperature-dependent energy level shift, i.e., temperature responsivity, being limited to -74 kHz/K. In this Letter, we take advantage of the magnetic field to regulate the energy level to enhance temperature sensitivity. The sensor is formed by adhering a micron-sized diamond on the end face of an optical fiber, and a small magnet is mounted at a certain distance with the diamond exploiting a cured polydimethylsiloxane block as the bridge. The temperature change leads to the variation of the distance between the diamond and the magnet, thus affecting the magnetic strength felt by the diamond. This finally contributes an additional temperature-induced energy level shift, giving rise to an enhanced sensitivity. Experimental results demonstrated the proposed scheme and achieved a 4.2-fold improvement in the temperature responsivity and a 2.1-fold enhancement in sensitivity. Moreover, the diamond and the fiber-optic integrated structure improve the portability of the sensor.

Targeted quantitative lipidomic uncovers lipid biomarkers for predicting the presence of compensated cirrhosis and discriminating decompensated cirrhosis from compensated cirrhosis.

OBJECTIVES: This study aimed to characterize serum lipid metabolism and identify potential biomarkers for compensated cirrhosis (CC) predicting and decompensated cirrhosis (DC) discrimination using targeted quantitative lipidomics and machine learning approaches. METHODS: Serum samples from a cohort of 120 participants was analyzed, including 90 cirrhosis patients (45 CC patients and 45 DC patients) and 30 healthy individuals. Lipid metabolic profiling was performed using targeted LC-MS/MS. Two machine learning methods, least absolute shrinkage and selection operator (LASSO), and random forest (RF) were applied to screen for candidate metabolite biomarkers. RESULTS: The metabolic profiling analysis showed a significant disruption in patients with CC and DC. Compared to the CC group, the DC group exhibited a significant upregulation in the abundance of glycochenodeoxycholic acid (GCDCA), glyco-ursodeoxycholic acid (GUDCA), glycocholic acid (GCA), phosphatidylethanolamine (PE), N-acyl-lyso-phosphatidylethanolamine (LNAPE), and triglycerides (TG), and a significant downregulation in the abundance of ceramides (Cer) and lysophosphatidylcholines (LPC). Machine learning identified 11 lipid metabolites (abbreviated as BMP11) as potential CC biomarkers with excellent prediction performance, with an AUC of 0.944, accuracy of 94.7 %, precision of 95.6 %, and recall of 95.6 %. For DC discrimination, eight lipids (abbreviated as BMP8) were identified, demonstrating strong efficacy, with an AUC of 0.968, accuracy of 92.2 %, precision of 88.0 %, and recall of 97.8 %. CONCLUSIONS: This study unveiled distinct lipidomic profiles in CC and DC patients and established robust lipid-based models for CC predicting and DC discrimination.

"Learn from Errors": Post-traumatic growth among second victims.

BACKGROUND: Second victims, defined as healthcare providers enduring emotional and psychological distress after patient safety incidents (PSIs). The potential for positive transformation through these experiences is underexplored but is essential for fostering a culture of error learning and enhancing patient care. OBJECTIVE: To explore the level and determinants of post-traumatic growth (PTG), applying the stress process model. METHODS: The study was conducted at a tertiary general hospital in Chongqing, China. A descriptive, cross-sectional study design was used. A total of 474 s victims were included. An online survey was conducted in November 2021 to assess various factors related to the second victim experience. These factors included PSIs (considered as stressors), coping styles, perceived threats, and social support (acting as mediators), as well as the outcomes of second victim syndrome (SVS) and PTG. Statistical description, correlation analysis, and structural equation modeling were utilized for the data analysis. A p-value ≤ 0.05 was considered to indicate statistical significance. RESULTS: The participants reported moderate distress (SVS = 2.84 ± 0.85) and PTG (2.72 ± 0.85). The total effects on SVS of perceived threat, negative coping, social support, positive coping, and PSIs were 0.387, 0.359, -0.355, -0.220, and 0.115, respectively, accounting for 47% of the variation in SVS. The total effects of social support, positive coping, and PSIs on PTG were 0.355, 0.203, and - 0.053, respectively, accounting for 19% of the variation in PTG. CONCLUSIONS: The study provides novel insights into the complex interplay between perceived threats, coping styles, and social support in facilitating PTG among second victims. By bolstering social support and promoting adaptive coping strategies, the adverse effects of PSIs can be mitigated, transforming them into opportunities for resilience and growth, and offering a fresh perspective on managing PSIs in healthcare settings.

Association of hypertension and depression with mortality: an exploratory study with interaction and mediation models.

BACKGROUND: The association of hypertension and depression with mortality has not been fully understood. We aimed to explore the possible independent or joint association of hypertension and depression with mortality. Their interaction effects on mortality and possible mediating role were also investigated. METHODS: Associations of hypertension, depression, and their interaction with all-cause and cardiovascular disease (CVD) mortality were evaluated using multivariate Cox proportional hazards regression models. The mediation analysis was conducted with a Sobel test. RESULTS: A total of 35152 participants were included in the final analysis. Hypertension and depression were independently associated with increased risk of all-cause and CVD mortality. The co-existence of hypertension and depression resulted in a 1.7-fold [95% confidence interval (CI): 1.3-2.1] increase in all-cause mortality and a 2.3-fold (95% CI: 1.4-3.7) increase in CVD mortality compared to those with neither of them. Hypertension and depression showed no significant multiplicative (P for interaction, 0.587) and additive interaction (P for relative excess risk of interaction, 0.243; P for Interaction on additive scale, 0.654) on all-cause mortality, as well as on CVD mortality. Depression did not mediate the relationship between hypertension and all-cause (Z=1.704, P=0.088) and CVD mortality (Z=1.547, P=0.122). Hypertension did not mediate the relationship between all-cause and CVD mortality as well. CONCLUSION: Hypertension and depression were related to all-cause and CVD mortality independently and the co-existence of them increased the risk of mortality. However, there is no interaction effect of them on mortality, and hypertension or depression did not mediate the association of each other with mortality.

Transcriptome Analysis Reveals the Mechanism by Which Exogenous Melatonin Treatment Delays Leaf Senescence of Postharvest Chinese Kale (Brassica oleracea var. alboglabra).

Melatonin, a pleiotropic small molecule, is employed in horticultural crops to delay senescence and preserve postharvest quality. In this study, 100 µM melatonin treatment delayed a decline in the color difference index h* and a*, maintaining the content of chlorophyll and carotenoids, thereby delaying the yellowing and senescence of Chinese kale. Transcriptome analysis unequivocally validates melatonin's efficacy in delaying leaf senescence in postharvest Chinese kale stored at 20 °C. Following a three-day storage period, the melatonin treatment group exhibited 1637 differentially expressed genes (DEGs) compared to the control group. DEG analysis elucidated that melatonin-induced antisenescence primarily governs phenylpropanoid biosynthesis, lipid metabolism, plant signal transduction, and calcium signal transduction. Melatonin treatment up-regulated core enzyme genes associated with general phenylpropanoid biosynthesis, flavonoid biosynthesis, and the α-linolenic acid biosynthesis pathway. It influenced the redirection of lignin metabolic flux, suppressed jasmonic acid and abscisic acid signal transduction, and concurrently stimulated auxin signal transduction. Additionally, melatonin treatment down-regulated RBOH expression and up-regulated genes encoding CaM, thereby influencing calcium signal transduction. This study underscores melatonin as a promising approach for delaying leaf senescence and provides insights into the mechanism of melatonin-mediated antisenescence in postharvest Chinese kale.

Insights into ZmWAKL in maize kernel development: genome-wide investigation and GA-mediated transcription.

BACKGROUND: The functional roles of the Wall Associated Kinase (WAK) and Wall Associated Kinase Like (WAKL) families in cellular expansion and developmental processes have been well-established. However, the molecular regulation of these kinases in maize development is limited due to the absence of comprehensive genome-wide studies. RESULTS: Through an in-depth analysis, we identified 58 maize WAKL genes, and classified them into three distinct phylogenetic clusters. Moreover, structural prediction analysis showed functional conservation among WAKLs across maize. Promoter analysis uncovered the existence of cis-acting elements associated with the transcriptional regulation of ZmWAKL genes by Gibberellic acid (GA). To further elucidate the role of WAKL genes in maize kernels, we focused on three highly expressed genes, viz ZmWAKL38, ZmWAKL42 and ZmWAKL52. Co-expression analyses revealed that their expression patterns exhibited a remarkable correlation with GA-responsive transcription factors (TF) TF5, TF6, and TF8, which displayed preferential expression in kernels. RT-qPCR analysis validated the upregulation of ZmWAKL38, ZmWAKL42, ZmWAKL52, TF5, TF6, and TF8 following GA treatment. Additionally, ZmWAKL52 showed significant increase of transcription in the present of TF8, with ZmWAKL52 localizing in both the plasma membrane and cell wall. TF5 positively regulated ZmWAKL38, while TF6 positively regulated ZmWAKL42. CONCLUSIONS: Collectively, these findings provide novel insights into the characterization and regulatory mechanisms of specific ZmWAKL genes involved in maize kernel development, offering prospects for their utilization in maize breeding programs.

High-sensitivity optical-fiber magnetic sensor based on diamond and magnetic flux concentrators.

Magnetic field detection exploiting nitrogen-vacancy (NV) centers in diamond has gained increasing attention and development in recent years. Combining diamond NV centers to optical fibers provides a way for achieving magnetic sensors with high integration and portability. Meanwhile, new methods or techniques are urgently desired to improve the detection sensitivity of such sensors. In this paper, we present an optical-fiber magnetic sensor based on the NV ensemble in diamond, and employ the well-designed magnetic flux concentrators to enhance the sensitivity up to 12 pT/Hz1/2, an outstanding level among the diamond-integrated optical-fiber magnetic sensors. The dependence of sensitivity on the key parameters including the size and gap width of the concentrators are investigated by simulations and experiments, based on which the predictions on the further enhancement of sensitivity to fT level are presented.

Influence factor analysis and prediction model of successful application of high-volume Foley Catheter for labor induction.

BACKGROUND: This study aimed to establish a clinical-based nomogram for predicting the success rate of high-volume Foley catheterization for labor induction. METHODS: This retrospective study included 1149 full-term pregnant women who received high-volume Foley catheterization for labor induction from January 2019 to December 2021 in Changshu No.1 People's Hospital. Univariate and multivariate logistic regression analyses were performed, in which the labor induction success was set as dependent variables and the characteristics (including age, height, weight, BMI, gravidity, parity, gestational age, uterine height, abdominal circumference, cervical Bishop score, amniotic fluid index, cephalic presentation, neonatal weight, pregnancy complications, etc.) were set as independent variables. A nomogram scoring model was established based on these risk factors, and a calibration curve was plotted to verify the predictive accuracy of the model. RESULTS: The success rate of labor induction was 83.55% (960/1149). Univariate analysis revealed that the risk factors associated with the success rate of high-volume Foley catheterization for labor induction were height, pregnancy, birth, age, weight, BMI, uterine height, abdominal circumference, and hypertension. Multivariate logistic regression analysis showed that age (OR = 0.950; 95% CI: 0.904 ~ 0.998), height (OR = 1.062; 95% CI: 1.026 ~ 1.100), BMI (OR = 0.871; 95% CI: 0.831 ~ 0.913), and parity (OR = 8.007; 95% CI: 4.483 ~ 14.303) were independent risk factors for labor induction success by high-volume Foley catheterization. The area under the curve (AUC) of the receiver operating characteristic (ROC) curve in the prediction model was 0.752 (95% CI 0.716 ~ 0.788). A nomogram was constructed based on the final multivariate analysis with a corrected C-index of 0.748, which indicated that the model was calibrated reasonably. CONCLUSION: Four risk factors were used to construct a nomogram to evaluate the success rate of high-volume Foley catheterization for labor induction. The nomogram provides a visual clinical tool to assist in the selection of the most appropriate mode of labor induction for pregnant women of different risk levels.

Hypoxia-induced miR-9 expression promotes ovarian cancer progression via activating PI3K/AKT/mTOR/GSK3ß signaling pathway.

Ovarian cancer (OC) is one of the most prevalent malignant tumors affecting women's life and health. Since OC has a poor prognosis due to extensive metastasis, there is a need to explore a new mechanism of OC metastasis. microRNAs (miRs) are single-stranded, non-coding RNAs. miR-9 has been reported to promote cancer and may provide a new strategy for OC diagnosis. The purpose of this study was to examine the function and underlying mechanism of miR-9 in OC. RT-qPCR was used to assess miR-9 expression levels. Transwell assays were used to determine the number of migrating and invading OC cells. The protein expression levels of the PI3K/AKT/mTOR/GSK3ß signaling pathway were examined using western blotting. The results informed that, when compared to normal ovarian tissues, miR-9 was remarkably expressed in OC tissues, and hypoxia might lead to overexpression of miR-9-5p while inhibiting miR-9 notably suppressed the migrating and invading cell numbers in OC cells. In vivo, miR-9-5p knockdown inhibited tumor growth in a subcutaneous nude mice model of SKOV3 cells. Our findings suggest that miR-9 could be an underlying oncogene in OC, opening up new avenues for OC diagnosis and treatment of OC by targeting miR-9.

Effects of sgRNAs, Promoters, and Explants on the Gene Editing Efficiency of the CRISPR/Cas9 System in Chinese Kale.

The CRISPR/Cas9 system is extensively used for plant gene editing. This study developed an efficient CRISPR/Cas9 system for Chinese kale using multiple sgRNAs and two promoters to create various CRISPR/Cas9 vectors. These vectors targeted BoaZDS and BoaCRTISO in Chinese kale protoplasts and cotyledons. Transient transformation of Chinese kale protoplasts was assessed for editing efficiency at three BoaZDS sites. Notably, sgRNA: Z2 achieved the highest efficiency (90%). Efficiency reached 100% when two sgRNAs targeted BoaZDS with a deletion of a large fragment (576 bp) between them. However, simultaneous targeting of BoaZDS and BoaCRTISO yielded lower efficiency. Transformation of cotyledons led to Chinese kale mutants with albino phenotypes for boazds mutants and orange-mottled phenotypes for boacrtiso mutants. The mutation efficiency of 35S-CRISPR/Cas9 (92.59%) exceeded YAO-CRISPR/Cas9 (70.97%) in protoplasts, and YAO-CRISPR/Cas9 (96.49%) surpassed 35S-CRISPR/Cas9 (58%) in cotyledons. These findings introduce a strategy for enhancing CRISPR/Cas9 editing efficiency in Chinese kale.

Sequencing and Analysis of Complete Chloroplast Genomes Provide Insight into the Evolution and Phylogeny of Chinese Kale (Brassica oleracea var. alboglabra).

Chinese kale is a widely cultivated plant in the genus Brassica in the family Brassicaceae. The origin of Brassica has been studied extensively, but the origin of Chinese kale remains unclear. In contrast to Brassica oleracea, which originated in the Mediterranean region, Chinese kale originated in southern China. The chloroplast genome is often used for phylogenetic analysis because of its high conservatism. Fifteen pairs of universal primers were used to amplify the chloroplast genomes of white-flower Chinese kale (Brassica oleracea var. alboglabra cv. Sijicutiao (SJCT)) and yellow-flower Chinese kale (Brassica oleracea var. alboglabra cv. Fuzhouhuanghua (FZHH)) via PCR. The lengths of the chloroplast genomes were 153,365 bp (SJCT) and 153,420 bp (FZHH) and both contained 87 protein-coding genes and eight rRNA genes. There were 36 tRNA genes in SJCT and 35 tRNA genes in FZHH. The chloroplast genomes of both Chinese kale varieties, along with eight other Brassicaceae, were analyzed. Simple sequence repeats, long repeats, and variable regions of DNA barcodes were identified. An analysis of inverted repeat boundaries, relative synonymous codon usage, and synteny revealed high similarity among the ten species, albeit the slight differences that were observed. The Ka/Ks ratios and phylogenetic analysis suggest that Chinese kale is a variant of B. oleracea. The phylogenetic tree shows that both Chinese kale varieties and B. oleracea var. oleracea were clustered in a single group. The results of this study suggest that white and yellow flower Chinese kale comprise a monophyletic group and that their differences in flower color arose late in the process of artificial cultivation. Our results also provide data that will aid future research on genetics, evolution, and germplasm resources of Brassicaceae.

Variation in the Main Health-Promoting Compounds and Antioxidant Capacity of Three Leafy Vegetables in Southwest China.

Malabar spinach (Basella alba), amaranth (Amaranthus tricolor), and sweet potato (Ipomoea batatas) are leafy vegetables found in Southwest China. The variation of chlorophyll, carotenoids, ascorbic acid, total flavonoids, phenolic compounds, and antioxidant capacity was studied in the leaves and stems of the three vegetables. The content of main health-promoting compounds and the antioxidant capacity in the leaves were higher than that in the stems, indicating that the leaves of the three vegetables possess greater nutritional value. The trend of total flavonoids in all three vegetables was similar to the trend of antioxidant capacity, suggesting that the total flavonoids may be the major antioxidants wihin these vegetables. Eight individual phenolic compounds were detected in three different vegetables. The most abundant levels of individual phenolic compounds in the leaves and stems of malabar spinach, amaranth, and sweet potato were 6'-O-feruloyl-d-sucrose (9.04 and 2.03 mg g-1 DW), hydroxyferulic acid (10.14 and 0.73 mg g-1 DW), and isorhamnetin-7-O-glucoside (34.93 and 6.76 mg g-1 DW), respectively. Sweet potato exhibited a higher total and individual phenolic compound content compared to malabar spinach and amaranth. Overall, the results demonstrate that the three leafy vegetables possess high nutritional value, and could be used not only for consumption but also in various other fields, including medicine and chemistry.

Coordinated regulation of starch synthesis in maize endosperm by microRNAs and DNA methylation.

Starch synthesis is an essential feature of crop filling, but knowledge of the molecular mechanisms regulating the expression of starch synthesis genes (SSGs) is currently limited to transcription factors (TFs). Here, we obtained transcriptome, small RNAome, and DNA methylome data from maize (Zea mays) endosperms during multiple developmental stages and established a regulatory network atlas of starch synthesis. Transcriptome analysis showed a sharp transition at 9-10 days after pollination, when genes involved in starch and sucrose metabolism are upregulated and starch accumulates rapidly. Expression pattern analysis established a comprehensive network between SSGs and TFs. During maize endosperm development, the miRNAs with preferential repression of the expression of TFs, particularly the TFs regulating SSG expression, were extensively downregulated. Specifically, ZmMYB138 and ZmMYB115 affected the transcriptional activities of Du1/Wx and Ae1/Bt2 genes at their respective promoter regions. Remarkably, the two TFs were negatively regulated by the copious expression of Zma-miR159k-3p at the post-transcriptional level. This suggests that miRNAs are important regulators of starch synthesis. Moreover, with the exclusion of the TFs, the expression of both SSGs and miRNAs was globally regulated by DNA methylation. Altogether, the present results (i) establish the regulatory functions of miRNAs and DNA methylation in starch synthesis and (ii) indicate that DNA methylation functions as a master switch.

A Wearable Diagnostic Assessment System vs. SNAP-IV for the auxiliary diagnosis of ADHD: a diagnostic test.

OBJECTIVE: We design a diagnostic test to evaluate the effectiveness and accuracy of A non-intrusive Wearable Diagnostic Assessment System versus SNAP-IV for auxiliary diagnosis of children with ADHD. METHODS: This study included 55 children aged 6-16 years who were clinically diagnosed with ADHD by DSM-5, and 55 healthy children (typically developing). Each subject completes 10 tasks on the WeDA system (Wearable Diagnostic Assessment System) and Parents of each subject complete the SNAP-IV scale. We will calculate the validity indexes, including sensitivity, specificity, Youden's index, likelihood ratio, and other indexes including predictive value, diagnostic odds ratio, diagnostic accuracy and area under the curve [AUC] to assess the effectiveness of the WeDA system as well as the SNAP-IV. RESULTS: The sensitivity (94.55% vs. 76.36%) and the specificity (98.18% vs. 80.36%) of the WeDA system were significantly higher than the SNAP-IV. The AUC of the WeDA system (0.964) was higher than the SNAP-IV (0.907). There is non-statistically significant difference between groups (p = 0.068), and both of them have high diagnostic accuracy. In addition, the diagnostic efficacy of the WeDA system was higher than that of SNAP-IV in terms of the Youden index, diagnostic accuracy, likelihood ratio, diagnostic odds ratio and predictive value. CONCLUSION: The advantages of the WeDA system in terms of diagnostic objectivity, scientific design and ease of operation make it a promising system for widespread use in clinical practice.

The synergistic effect of depression and moderate chronic kidney disease on the all-cause and cardiovascular disease mortality among adults: a retrospective cohort study.

BACKGROUND: The relationship between the coexistence of depression and moderate chronic kidney disease (CKD) and mortality is unclear. We aimed to investigate whether there is a synergistic effect of depression and moderate CKD on the all-cause and cardiovascular disease (CVD) mortality among adults. METHODS: We studied 24,412 participants from the National Health and Nutrition Examination Survey 2005-2014 with a mortality follow-up assessment in 2015. Four groups were created based on depression and CKD status: Group 1, no depression and no CKD; Group 2, depression present and no CKD; Group 3: no depression and CKD present; Group 4: depression present and CKD present. Moderate CKD was defined as an estimated glomerular filtration rate of 15-59 mL/min/1.73 m2 (Stage 3-4) or one-time urine albumin-to-creatinine ratio ≥ 30 mg/g. Depression was defined as the 9-item Patient Health Questionnaire score of 10 or more. Cox proportional hazards regression models were used to calculate the multivariate-adjusted hazard ratios (HRs) of death for Group 4 with other groups. RESULTS: Over a mean follow-up of 5.8 years, 1783 deaths were documented, including 338 deaths from CVD. The HR for all-cause mortality in Group 4 was 3.62 (95% CI: 2.69-4.87), 2.99 (1.92-4.66), and 1.75 (1.29-2.37) when compared with Group 1, 2, and 3, respectively. The HR for CVD mortality in Group 4 was 3.89 (1.68-9.00), 1.90 (0.86-4.21), and 1.97 (1.17-3.32) when compared with Group 1, 2, and 3, respectively. CONCLUSIONS: There might be a synergistic effect of depression and moderate CKD on all-cause mortality. Moreover, depression might increase the risk of CVD mortality in individuals with moderate CKD.

Comparative Study of Starch Phosphorylase Genes and Encoded Proteins in Various Monocots and Dicots with Emphasis on Maize.

Starch phosphorylase (PHO) is a multimeric enzyme with two distinct isoforms: plastidial starch phosphorylase (PHO1) and cytosolic starch phosphorylase (PHO2). PHO1 specifically resides in the plastid, while PHO2 is found in the cytosol. Both play a critical role in the synthesis and degradation of starch. This study aimed to report the detailed structure, function, and evolution of genes encoding PHO1 and PHO2 and their protein ligand-binding sites in eight monocots and four dicots. "True" orthologs of PHO1 and PHO2 of Oryza sativa were identified, and the structure of the enzyme at the protein level was studied. The genes controlling PHO2 were found to be more conserved than those controlling PHO1; the variations were mainly due to the variable sequence and length of introns. Cis-regulatory elements in the promoter region of both genes were identified, and the expression pattern was analyzed. The real-time quantitative polymerase chain reaction indicated that PHO2 was expressed in all tissues with a uniform pattern of transcripts, and the expression pattern of PHO1 indicates that it probably contributes to the starch biosynthesis during seed development in Zea mays. Under abscisic acid (ABA) treatment, PHO1 was found to be downregulated in Arabidopsis and Hordeum vulgare. However, we found that ABA could up-regulate the expression of both PHO1 and PHO2 within 12 h in Zea mays. In all monocots and dicots, the 3D structures were highly similar, and the ligand-binding sites were common yet fluctuating in the position of aa residues.

Genome-wide identification of ZmSnRK2 genes and functional analysis of ZmSnRK2.10 in ABA signaling pathway in maize (Zea mays L).

BACKGROUND: Phytohormone abscisic acid (ABA) is involved in the regulation of a wide range of biological processes. In Arabidopsis, it has been well-known that SnRK2s are the central components of the ABA signaling pathway that control the balance between plant growth and stress response, but the functions of ZmSnRK2 in maize are rarely reported. Therefore, the study of ZmSnRK2 is of great importance to understand the ABA signaling pathways in maize. RESULTS: In this study, 14 ZmSnRK2 genes were identified in the latest version of maize genome database. Phylogenetic analysis revealed that ZmSnRK2s are divided into three subclasses based on their diversity of C-terminal domains. The exon-intron structures, phylogenetic, synteny and collinearity analysis indicated that SnRK2s, especially the subclass III of SnRK2, are evolutionally conserved in maize, rice and Arabidopsis. Subcellular localization showed that ZmSnRK2 proteins are localized in the nucleus and cytoplasm. The RNA-Seq datasets and qRT-PCR analysis showed that ZmSnRK2 genes exhibit spatial and temporal expression patterns during the growth and development of different maize tissues, and the transcript levels of some ZmSnRK2 genes in kernel are significantly induced by ABA and sucrose treatment. In addition, we found that ZmSnRK2.10, which belongs to subclass III, is highly expressed in kernel and activated by ABA. Overexpression of ZmSnRK2.10 partially rescued the ABA-insensitive phenotype of snrk2.2/2.3 double and snrk2.2/2.3/2.6 triple mutants and led to delaying plant flowering in Arabidopsis. CONCLUSION: The SnRK2 gene family exhibits a high evolutionary conservation and has expanded with whole-genome duplication events in plants. The ZmSnRK2s expanded in maize with whole-genome and segmental duplication, not tandem duplication. The expression pattern analysis of ZmSnRK2s in maize offers important information to study their functions. Study of the functions of ZmSnRK.10 in Arabidopsis suggests that the ABA-dependent members of SnRK2s are evolutionarily conserved in plants. Our study elucidated the structure and evolution of SnRK2 genes in plants and provided a basis for the functional study of ZmSnRK2s protein in maize.

Mutations in ASH1L confer susceptibility to Tourette syndrome.

Tourette syndrome (TS) is a childhood-onset neuropsychiatric disorder characterized by repetitive motor movements and vocal tics. The clinical manifestations of TS are complex and often overlap with other neuropsychiatric disorders. TS is highly heritable; however, the underlying genetic basis and molecular and neuronal mechanisms of TS remain largely unknown. We performed whole-exome sequencing of a hundred trios (probands and their parents) with detailed records of their clinical presentations and identified a risk gene, ASH1L, that was both de novo mutated and associated with TS based on a transmission disequilibrium test. As a replication, we performed follow-up targeted sequencing of ASH1L in additional 524 unrelated TS samples and replicated the association (P value = 0.001). The point mutations in ASH1L cause defects in its enzymatic activity. Therefore, we established a transgenic mouse line and performed an array of anatomical, behavioral, and functional assays to investigate ASH1L function. The Ash1l+/- mice manifested tic-like behaviors and compulsive behaviors that could be rescued by the tic-relieving drug haloperidol. We also found that Ash1l disruption leads to hyper-activation and elevated dopamine-releasing events in the dorsal striatum, all of which could explain the neural mechanisms for the behavioral abnormalities in mice. Taken together, our results provide compelling evidence that ASH1L is a TS risk gene.

The efficacy of addition of Tenofovir Disoproxil Fumarate to Peg-IFNα-2b is superior to the addition of Entecavir in HBeAg positive CHB patients with a poor response after 12 weeks of Peg-IFNα-2b treatment alone.

Background: There are limited data regarding the efficacy of addition of entecavir (ETV) or tenofovir disoproxil fumarate (TDF) to Peg-IFNα-2b in HBeAg positive chronic hepatitis B (CHB) patients without early response to Peg-IFNα-2b. In this study, we aimed to evaluate the efficacy of ETV and TDF in HBeAg positive CHB patients who had a poor response to Peg-INFα-2b at the end of 12 weeks of monotherapy. Methods: A total of 40 HBeAg-positive CHB patients who were naive to antiviral therapy were recruited. The patients received a subcutaneous injection of Peg-IFNα-2b (180 µg) once a week for 12 weeks. However, the patients had a poor response to Peg-INFα-2b at the end of the 12-week-period monotherapy. The patients were then divided into two therapeutic protocol groups: (1) Group A: Patients received Peg-IFNα-2b (180 µg) subcutaneously weekly and ETV (0.5 mg) orally once daily for 48 weeks; (2) Group B: Patients received Peg-IFNα-2b (180 µg) subcutaneously weekly and TDF (300 mg) orally once daily for 48 weeks. The therapeutic efficacy was evaluated. Blood samples were collected at baseline and every 12 weeks. Routine biochemical tests including ALT, AST, etc. were measured by automated biochemical technique. HBV DNA was quantified using the TaqMan PCR assay. The levels of HBsAg, HBsAb, HBeAg, HBeAb and HBcAb were measured using a commercial chemiluminescent microparticle immunoassay. Results: The HBsAg level declined rapidly in both two treatment groups during the first 12 weeks and declined gradually in the next 36 weeks. At week 48, the mean ΔHBsAg level in Peg-IFNα-2b+TDF group was significantly higher than that in Peg-IFNα-2b +ETV group (-1.799 ± 0.3063 vs. -1.078 ± 0.2028, P=0.0491). The HBeAg loss rate was significantly higher in TDF add-on group than that in ETV add-on group at week 48 (40% vs. 10%, P=0.028). At week 48, the proportions of patients with undetectable HBV DNA (<500 IU/mL) were 80% (16 out of 20) and 95% (19 out of 20) in Peg-IFNα-2b+ETV group and Peg-IFNα-2b+TDF group, respectively. Conclusions: This real world study demonstrated that the efficacy of addition of TDF to Peg-IFNα-2b is superior to the efficacy of addition of ETV to Peg-IFNα-2b in HBeAg positive CHB patients with a poor response after 12 weeks of Peg-IFNα-2b treatment alone. However, this present study also requires a larger sample size study to verify in the future.