ι-Carrageenan catabolism is initiated by key sulfatases in the marine bacterium Pseudoalteromonas haloplanktis LL1.

Marine bacteria contribute substantially to cycle macroalgae polysaccharides in marine environments. Carrageenans are the primary cell wall polysaccharides of red macroalgae. The carrageenan catabolism mechanism and pathways are still largely unclear. Pseudoalteromonas is a representative bacterial genus that can utilize carrageenan. We previously isolated the strain Pseudoalteromonas haloplanktis LL1 that could grow on ι-carrageenan but produce no ι-carrageenase. Here, through a combination of bioinformatic, biochemical, and genetic analyses, we determined that P. haloplanktis LL1 processed a desulfurization-depolymerization sequential pathway for ι-carrageenan utilization, which was initiated by key sulfatases PhSulf1 and PhSulf2. PhSulf2 acted as an endo/exo-G4S (4-O-sulfation-ß-D-galactopyranose) sulfatase, while PhSulf1 was identified as a novel endo-DA2S sulfatase that could function extracellularly. Because of the unique activity of PhSulf1 toward ι-carrageenan rather than oligosaccharides, P. haloplanktis LL1 was considered to have a distinct ι-carrageenan catabolic pathway compared to other known ι-carrageenan-degrading bacteria, which mainly employ multifunctional G4S sulfatases and exo-DA2S (2-O-sulfation-3,6-anhydro-α-D-galactopyranose) sulfatase for sulfate removal. Furthermore, we detected widespread occurrence of PhSulf1-encoding gene homologs in the global ocean, indicating the prevalence of such endo-acting DA2S sulfatases as well as the related ι-carrageenan catabolism pathway. This research provides valuable insights into the enzymatic processes involved in carrageenan catabolism within marine ecological systems.IMPORTANCECarrageenan is a type of linear sulfated polysaccharide that plays a significant role in forming cell walls of marine algae and is found extensively distributed throughout the world's oceans. To the best of our current knowledge, the ι-carrageenan catabolism in marine bacteria either follows the depolymerization-desulfurization sequential process initiated by ι-carrageenase or starts from the desulfurization step catalyzed by exo-acting sulfatases. In this study, we found that the marine bacterium Pseudoalteromonas haloplanktis LL1 processes a distinct pathway for ι-carrageenan catabolism employing a specific endo-acting DA2S-sulfatase PhSulf1 and a multifunctional G4S sulfatase PhSulf2. The unique PhSulf1 homologs appear to be widely present on a global scale, indicating the indispensable contribution of the marine bacteria containing the distinct ι-carrageenan catabolism pathway. Therefore, this study would significantly enrich our understanding of the molecular mechanisms underlying carrageenan utilization, providing valuable insights into the intricate roles of marine bacteria in polysaccharide cycling in marine environments.

A wild rice CSSL population facilitated identification of salt tolerance genes and rice germplasm innovation.

Salt stress is one of the major factors that limits rice production. Therefore, identification of salt-tolerant alleles from wild rice is important for rice breeding. In this study, we constructed a set of chromosome segment substitution lines (CSSLs) using wild rice as the donor parent and cultivated rice Nipponbare (Nip) as the recurrent parent. Salt tolerance germinability (STG) was evaluated, and its association with genotypes was determined using this CSSL population. We identified 17 QTLs related to STG. By integrating the transcriptome and genome data, four candidate genes were identified, including the previously reported AGO2 and WRKY53. Compared with Nip, wild rice AGO2 has a structure variation in its promoter region and the expression levels were upregulated under salt treatments; wild rice WRKY53 also has natural variation in its promoter region, and the expression levels were downregulated under salt treatments. Wild rice AGO2 and WRKY53 alleles have combined effects for improving salt tolerance at the germination stage. One CSSL line, CSSL118 that harbors these two alleles was selected. Compared with the background parent Nip, CSSL118 showed comprehensive salt tolerance and higher yield, with improved transcript levels of reactive oxygen species scavenging genes. Our results provided promising genes and germplasm resources for future rice salt tolerance breeding.

Potential causal associations between leisure sedentary behaviors, physical activity, sleep traits, and myopia: a Mendelian randomization study.

BACKGROUND: Myopia is the most prevalent refractive error and a growing global health concern that significantly affects visual function. Researchers have recently emphasized considerably on the influence of lifestyle on myopia incidence and development. This study investigates the relationship between leisure sedentary behaviors (LSB)/physical activity (PA)/sleep traits and myopia. METHODS: LSB, PA, and sleep trait-associated genetic variants were used as instrument variables in a Mendelian randomization (MR) study to examine their causal effects on myopia. Summary genome-wide association studies (GWASs) statistical data for LSB and PA were obtained from UK Biobank, and the data of sleep traits was obtained from UK Biobank, UK Biobank and 23andMe, and FinnGen. We used summary statistics data for myopia from MRC IEU. The MR analyses was performed using the inverse variance-weighted (IVW), MR-Egger, weighted median, and MR Pleiotropy RESidual Sum and Outlier methods. RESULTS: Computer use was genetically predicted to increase the myopia risk [IVW odds ratio (OR) = 1.057; 95% confidence interval (CI), 1.038-1.078; P = 7.04 × 10- 9]. The self-reported moderate-to-vigorous physical activity (MVPA) (IVW OR = 0.962; 95% CI, 0.932-0.993; P = 1.57 × 10- 2) and television watching (IVW OR = 0.973; 95% CI, 0.961-0.985, P = 1.93 × 10- 5) were significantly associated with a lower myopia risk. However, genetically predicted sleep traits or accelerometer-measured physical activity had no significant associations with myopia. CONCLUSION: Our results indicated that computer use is a risk factor for myopia, whereas television watching and MVPA may protect against myopia. These findings shed new light on possible strategies for reducing the prevalence of myopia.

Vapor isotopic evidence for the worsening of winter air quality by anthropogenic combustion-derived water.

Anthropogenic combustion-derived water (CDW) may accumulate in an airshed due to stagnant air, which may further enhance the formation of secondary aerosols and worsen air quality. Here we collected three-winter-season, hourly resolution, water-vapor stable H and O isotope compositions together with atmospheric physical and chemical data from the city of Xi'an, located in the Guanzhong Basin (GZB) in northwestern China, to elucidate the role of CDW in particulate pollution. Based on our experimentally determined water vapor isotope composition of the CDW for individual and weighted fuels in the basin, we found that CDW constitutes 6.2% of the atmospheric moisture on average and its fraction is positively correlated with [PM2.5] (concentration of particulate matter with an aerodynamic diameter less than 2.5 µm) as well as relative humidity during the periods of rising [PM2.5]. Our modeling results showed that CDW added additional average 4.6 µg m-3 PM2.5 during severely polluted conditions in the GZB, which corresponded to an average 5.1% of local anthropogenic [PM2.5] (average at ∼91.0 µg m-3). Our result is consistent with the proposed positive feedback between the relative humidity and a moisture sensitive air-pollution condition, alerting to the nontrivial role of CDW when considering change of energy structure such as a massive coal-to-gas switch in household heating in winter.

Genome-Wide Identification and Expression Analysis of Malate Dehydrogenase Gene Family in Sweet Potato and Its Two Diploid Relatives.

Malate dehydrogenase (MDH; EC 1.1.1.37) plays a vital role in plant growth and development as well as abiotic stress responses, and it is widely present in plants. However, the MDH family genes have not been explored in sweet potato. In this study, nine, ten, and ten MDH genes in sweet potato (Ipomoea batatas) and its two diploid wild relatives, Ipomoea trifida and Ipomoea triloba, respectively, were identified. These MDH genes were unevenly distributed on seven different chromosomes among the three species. The gene duplications and nucleotide substitution analysis (Ka/Ks) revealed that the MDH genes went through segmental duplications during their evolution under purifying selection. A phylogenetic and conserved structure divided these MDH genes into five subgroups. An expression analysis indicated that the MDH genes were omni-presently expressed in distinct tissues and responded to various abiotic stresses. A transcription factor prediction analysis proved that Dof, MADS-box, and MYB were the main transcription factors of sweet potato MDH genes. These findings provide molecular features of the MDH family in sweet potato and its two diploid wild relatives, which further supports functional characterizations.

Impaired vessel relaxation response and increased infarct size in smooth muscle cannabinoid receptor 1 knockout mice.

Cannabinoids are reported to regulate cardiovascular functions. Cannabinoid receptors 1 (CB1Rs) are widely expressed in both the neuronal system and vascular system, but the contribution of CB1Rs in vascular smooth muscle (CB1RSM) to cardiovascular functions is not clear yet. In this research, we analyzed the effects of CB1RSM on blood pressure, vasoconstriction, and vasodilation abilities by using conditionally CB1R knockout mice (CB1RSMKO). The results show no significant difference in basal blood pressure between the conscious CB1RSMKO and control mice, indicating that CB1RSM is not essential for basal blood pressure maintenance. The constriction of the CB1RSMKO mesenteric artery in vitro was not significantly altered compared with that of the control mice. In contrast, the relaxation to CB1R agonist 2-AG or WIN55212-2 was decreased in CB1RSMKO vessels, suggesting that activation of CB1RSM mediates the vasodilation effect of cannabinoids. Ischemia stroke mouse model was used to further identify the potential function of CB1RSM in pathological conditions, and the results showed that the infarct volume in CB1RSMKO mice is significantly increased compared with the control littermates. These results suggest that vascular CB1R may not play a central role in basal vascular health maintenance but is protective in ischemia states, such as stroke. The protection function may be mediated, at least partly, by the relaxation effect of CB1RSM-dependent activities of endocannabinoids.

Epigenetics in psoriasis: perspective of DNA methylation.

Psoriasis is a chronic inflammatory skin disease characterized by excessive proliferation of keratinocytes (KCs). Onset of psoriasis is related to genetic, immune and environmental factors. The environment can interact with the genome through epigenetic modifications, including DNA methylation, and this modification is involved in the pathogenesis of psoriasis. In addition to a skin disease, psoriasis is also considered a systemic disease. We reviewed the current literature of psoriatic DNA methylation for studies from several aspects on the DNA methylation distribution patterns in different tissues/cells, single-nucleotide polymorphisms, and candidate disease genes and identified target genes regulated by DNA methylation that have been directly/indirectly validated. This review contributes to a comprehensive understanding of the important a role that DNA methylation plays in psoriasis from a holistic perspective and will promote the implementation of DNA methylation in diagnostic and therapeutic strategies for psoriatic patients.

Serum N-glycan profiling as a diagnostic biomarker for the identification and assessment of psoriasis.

BACKGROUND: Glycosylation is an important post-translational modification of protein. The change in glycosylation is involved in the occurrence and development of various diseases, and this study verified that N-glycan markers might be a diagnostic marker in psoriasis. METHODS: A total of 76 psoriasis patients were recruited. We used Psoriasis Area Severity Index (PASI) scores to evaluate the state of psoriasis, 41 of whom were divided into three subgroups: mild, moderate, and severe. At the same time, 76 healthy subjects were enrolled as a control group. We used DNA sequencer-assisted fluorophore-assisted carbohydrate electrophoresis (DSA-FACE) to analyze serum N-glycan profiling. RESULTS: Compared with the healthy controls, the relative abundance of structures in peaks 5(NA2), 9(NA3Fb), 11(NA4), and 12(NA4Fb) was elevated (p < .05), while that in peaks 3(NG1A2F), 4(NG1A2F), 6(NA2F), and 7(NA2FB) was decreased (p < .05) in the psoriasis group. The abundance of peak 5 (NA2) increased gradually with the aggravation of disease severity though there was no statistically significant, was probably correlated with the disease severity. The best area under the receiver operating characteristic (ROC) curve (AUC) of the logistic regression model (PglycoA) to diagnose psoriasis was 0.867, with a sensitivity of 72.37%, a specificity of 85.53%, a positive predictive value(PPV) of 83.33%, a negative predictive value(NPV) of 75.58%, and an accuracy of 78.95%. CONCLUSIONS: Our study indicated that the N-glycan-based diagnostic model would be a new, valuable, and noninvasive alternative for diagnosing psoriasis. Furthermore, the characteristic distinctive N-glycan marker might be correlated with the severity gradation of the psoriasis disease.

Applying probability calibration to ensemble methods to predict 2-year mortality in patients with DLBCL.

BACKGROUND: Under the influences of chemotherapy regimens, clinical staging, immunologic expressions and other factors, the survival rates of patients with diffuse large B-cell lymphoma (DLBCL) are different. The accurate prediction of mortality hazards is key to precision medicine, which can help clinicians make optimal therapeutic decisions to extend the survival times of individual patients with DLBCL. Thus, we have developed a predictive model to predict the mortality hazard of DLBCL patients within 2 years of treatment. METHODS: We evaluated 406 patients with DLBCL and collected 17 variables from each patient. The predictive variables were selected by the Cox model, the logistic model and the random forest algorithm. Five classifiers were chosen as the base models for ensemble learning: the naïve Bayes, logistic regression, random forest, support vector machine and feedforward neural network models. We first calibrated the biased outputs from the five base models by using probability calibration methods (including shape-restricted polynomial regression, Platt scaling and isotonic regression). Then, we aggregated the outputs from the various base models to predict the 2-year mortality of DLBCL patients by using three strategies (stacking, simple averaging and weighted averaging). Finally, we assessed model performance over 300 hold-out tests. RESULTS: Gender, stage, IPI, KPS and rituximab were significant factors for predicting the deaths of DLBCL patients within 2 years of treatment. The stacking model that first calibrated the base model by shape-restricted polynomial regression performed best (AUC = 0.820, ECE = 8.983, MCE = 21.265) in all methods. In contrast, the performance of the stacking model without undergoing probability calibration is inferior (AUC = 0.806, ECE = 9.866, MCE = 24.850). In the simple averaging model and weighted averaging model, the prediction error of the ensemble model also decreased with probability calibration. CONCLUSIONS: Among all the methods compared, the proposed model has the lowest prediction error when predicting the 2-year mortality of DLBCL patients. These promising results may indicate that our modeling strategy of applying probability calibration to ensemble learning is successful.

Efficacy and safety of Tripterygium wilfordii Hook. f. for oral lichen planus: Evidence from 18 randomized controlled trials.

Glycosides from the roots of Tripterygium wilfordii Hook. f. are used for the treatment of oral lichen planus (OLP), a chronic inflammatory disease affecting the oral mucosa. To investigate the effectiveness and safety of Tripterygium glycosides (TGs) for OLP treatment, we conducted a systematic review of 18 randomized controlled trials, comprising 1,339 participants, from international and Chinese databases. We evaluated outcomes of TGs alone or in combination with conventional treatments. In combination with topical glucocorticoids (TGCs), including triamcinolone acetonide and prednisone, the total effectiveness rate (risk ratio [RR], 1.17; 95% confidence interval [CI], 1.09-1.25; p < .00001), symptom score reducing index (mean difference [MD], -2.44; 95% CI, -3.12 to -1.77; p < .0001), and visual analog scale score (MD, -1.61; 95% CI, -2.22 to -1.00; p < .0001) were significantly improved. Patients treated with TGs combined with TGCs experienced lower recurrence rates (RR, 0.37; 95% CI, 0.18-0.76; p = 0.007). The occurrence of adverse events was not significantly different between the TGs groups and controls. The combination of TG and TGCs improved clinical efficacy and reduced recurrence without increasing the risk of adverse events. A high-quality multicenter clinical study is needed to corroborate these findings.

[Effect of ethanolic extract of Polygonum cuspidatum on acute gouty arthritis in mice through NLRP3/ASC/caspase-1 axis].

The aim of this paper was to study the effect and mechanism of alcohol extract from Polygonum cuspidatum(PCE) on acute gouty arthritis in C57 BL/6 mice through NLRP3/ASC/caspase-1 axis. The model mice which injected with ankle joint injection of sodium urate crystals(MSU) were orally administrated with three different concentration of PCE, with colchicine as positive control. HE staining was used for observing the morphological changes of synovial tissue; concentration of IL-1ß, IL-6 and TNF-α secreted by synovial tissue of the ankle joint were detected by ELISA; mRNA and protein expression of NLRP3, ASC and caspase-1 in synovial tissue were detected by RT-PCR and Western blot respectively. The results showed that the swelling degree of ankle joint in model mice were significantly elevated; expression of IL-1ß, IL-6 and TNF-α were significantly increased; mRNA and protein expression of NLRP3, ASC and caspase-1 also significant increase, compared with normal control group. The swelling degree of ankle joint significantly relief; expression of IL-1ß, IL-6 and TNF-α in joint synovium significantly decrease; mRNA and protein expression of NLRP3, ASC and caspase-1 were significantly decrease in PCE treatment group compared with model group. Our research implied that alcohol extract from P. cuspidatum had positive effect on acute gouty arthritis in mice, and the regulation of NLRP3/ASC/caspase-1 axis may be its mechanism.

Riemannian Spatio-Temporal Features of Locomotion for Individual Recognition.

Individual recognition based on skeletal sequence is a challenging computer vision task with multiple important applications, such as public security, human⁻computer interaction, and surveillance. However, much of the existing work usually fails to provide any explicit quantitative differences between different individuals. In this paper, we propose a novel 3D spatio-temporal geometric feature representation of locomotion on Riemannian manifold, which explicitly reveals the intrinsic differences between individuals. To this end, we construct mean sequence by aligning related motion sequences on the Riemannian manifold. The differences in respect to this mean sequence are modeled as spatial state descriptors. Subsequently, a temporal hierarchy of covariance are imposed on the state descriptors, making it a higher-order statistical spatio-temporal feature representation, showing unique biometric characteristics for individuals. Finally, we introduce a kernel metric learning method to improve the classification accuracy. We evaluated our method on two public databases: the CMU Mocap database and the UPCV Gait database. Furthermore, we also constructed a new database for evaluating running and analyzing two major influence factors of walking. As a result, the proposed approach achieves promising results in all experiments.

Evaluation of serum autoantibodies against tumor-associated antigens as biomarkers in lung cancer.

We evaluated autoantibodies against nine tumor-associated antigens, including p62, p16, Koc, p53, Cyclin B1, Cyclin E, Survivin, HCC1, and RalA as serological markers in lung cancer. Enzyme-linked immunosorbent assay (ELISA) was used to detect autoantibodies in sera from 50 lung cancer patients and 42 normal controls. Then, four tumor-associated antigens of higher values were selected and validated in sera from validation group. Western blot and serum absorption test were used to confirm positive findings from ELISA. When cutoff values were set as mean optical density values plus 3 standard deviation of normal controls, the positive rate of autoantibodies against four tumor-associated antigens (Survivin, Cyclin B1, HCC1, and p53) reached 32%, 20%, 22%, and 18%, with area under the curve values of 0.653, 0.767, 0.622, and 0.623 in sera from 50 lung cancer, respectively (all p < 0.05). Results from the validation group confirmed the results. When lung cancer patients were divided by their clinicopathological characteristics into different subgroups, we have found that serum anti-Cyclin B1 and anti-HCC1 autoantibodies increased in stages 1, 2, and 3 lung cancer; anti-Survivin autoantibodies increased in stages 2 and 3 lung cancer; and anti-p53 autoantibody only increased in stage 1 when compared with their corresponding levels in controls (all p < 0.05). Serum anti-Cyclin B1 and anti-Survivin autoantibodies increased with disease histological grade 2 and 3 (both p < 0.05). And higher serum level of anti-p53 autoantibodies is positively associated with tumor size. Parallel utilization of these four anti-tumor-associated antigens (any positive) can increase sensitivity to 65.0% at 100% specificity with area under the curve of 0.908 ( p < 0.001) in lung cancer detection in validation group. Our results suggest that autoantibodies against these four tumor-associated antigens have higher values in lung cancer detection, and serum anti-Cyclin-B1 has the potential to serve as novel non-invasive biomarkers in early-stage lung cancer.

Serum autoantibodies against a panel of 15 tumor-associated antigens in the detection of ovarian cancer.

In this study, enzyme-linked immunosorbent assay has been used to examine the frequencies of serum autoantibodies against two candidate tumor-associated antigens intensively selected from the Human Protein Atlas database, in combination with 13 tumor-associated antigens available from our lab in sera from 44 OC patients and 50 normal healthy controls. Conventional evaluation (mean + 3SD as the cutoff value to determine a positive reactivity), receiver operating characteristic curve analyses, and classification tree analysis were further used to evaluate the diagnostic performance of autoantibodies against these tumor-associated antigens (anti-tumor-associated antigens) in ovarian cancer. For single anti-tumor-associated antigen, when the cutoff values were set as mean + 3SD of normal healthy controls, NPM1, MDM2, PLAT, p53, and c-Myc could achieve sensitivity higher than 20% at 98% specificity. Combinational utilization of autoantibodies against MDM2, PLAT, NPM1, 14-3-3 Zeta, p53, and RalA achieved the optimal diagnostic performance with 72.7% sensitivity at 96% specificity. Receiver operating characteristic curve analysis showed that the area under the receiver operating characteristic curves of autoantibodies against c-Myc, NPM1, MDM2, p16, p53, and 14-3-3 Zeta were greater than 0.80. This indicated that these tumor-associated antigens held high potential to serve as diagnostic biomarkers in ovarian cancer detection. Decision tree analysis indicated that anti-c-Myc held high potential in the detection of ovarian cancer. Further studies are warranted to validate the diagnostic performance of these anti-tumor-associated antigens with high area under the receiver operating characteristic curve, including autoantibodies against c-Myc, MDM2, PLAT, NPM1, 14-3-3 Zeta, p53, and RalA.

Contribution of long duration of undiagnosed bipolar disorder to high frequency of relapse: A naturalistic study in China.

BACKGROUND: With attention to misdiagnosis of bipolar disorder (BP), long duration of undiagnosed bipolar disorder (DUBP) had been reported recently in years. This study aims to investigate the contributions of long DUBP to the frequency of relapse in bipolar patients, and explore affect factors of DUBP. METHOD: From 26 hospitals throughout China, 3896 participants diagnosed with BP according to International Classification of Diseases 10th criteria were enrolled in this study. Socio-demographic and clinical data were collected from medical records and specific questionnaires through clinical interviews with patients and their relatives. RESULTS: (1) Our results showed that the mean of DUBP was 40.52months. In total, 779 patients (19.995%) reported DUBP greater than 5years, and 1931 patients (49.564%) reported their DUBP greater than 2years. The number of mood episodes was averaged 5.44, and the frequency ratio of (hypo) mania to depressive episodes was 1.49 (3.27/2.19). (2) Multiple linear regression analysis revealed that DUBP was significantly contributed to the number of relapse (Beta=0.072, p<0.001) after considering the confounding including gender, age at study entry, age of onset, age of first (hypo) manic episodes, age of first depressive episodes, type of first episodes and family history of mental illness. (3) Factors including age at the study entry (Beta=0.526, p<0.001), age of onset (Beta=-1.654, p<0.001), age of first (hypo) manic episode (Beta=0.348, p<0.001), age of first depressive episode (Beta=0.983, p<0.001), depression as the type of first episode (Beta=0.058, p<0.001) and family history of mental illness (Beta=0.029, p<0.05) were significantly contributed to long DUBP. CONCLUSION: It was concluded that long DUBP might lead to high frequent relapse in bipolar patients. The factors correlated with long DUBP include older age, early age of onset, depression as the type of first episode and family history of mental illness. The findings of our study suggest emergency task to early reorganization of bipolar disorder, and improving clinicians' recognition of bipolar disorder from patients with depressive episodes, especially in children and adolescents.

Cu(OAc)2-promoted reaction of [60]fullerene with primary amines or diamines.

The Cu(OAc)2-promoted reaction of C60 with easily available primary amines allows the concise preparation of aziridinofullerenes. Both alkyl and aryl amines are suitable in this reaction. Moreover, the Cu(OAc)2-promoted reaction of C60 with diamines affords C60-fused cyclic 1,2-diaminated fullerenes.

Lewis base-catalyzed reaction of aziridinofullerene with ureas for the preparation of fulleroimidazolidinones.

The Lewis base-catalyzed double nucleophilic substitution reaction of N-tosylaziridinofullerene with various ureas allows the easy preparation of fulleroimidazolidinones with a high tolerance for functional groups. Alkyl-substituted ureas show better reactivity than aryl-substituted ureas.