ABSTRACT
Alternative splicing (AS) is a key transcriptional regulation pathway. Recent studies have shown that AS events are associated with the occurrence of complex diseases. Various computational approaches have been developed for the detection of disease-associated AS events. In this review, we first describe the metrics used for quantitative characterization of AS events. Second, we review and discuss the three types of methods for detecting disease-associated splicing events, which are differential splicing analysis, aberrant splicing detection and splicing-related network analysis. Third, to further exploit the genetic mechanism of disease-associated AS events, we describe the methods for detecting genetic variants that potentially regulate splicing. For each type of methods, we conducted experimental comparison to illustrate their performance. Finally, we discuss the limitations of these methods and point out potential ways to address them. We anticipate that this review provides a systematic understanding of computational approaches for the analysis of disease-associated splicing.
Subject(s)
Alternative Splicing , Computational BiologyABSTRACT
Reflective mirrors are the key imaging components of space-borne telescopes, which require a high lightweight ratio integrated with excellent optical properties. In this context, a novel, to our knowledge, 2.5D centroidal Voronoi tessellation (CVT) generation methodology is proposed for designing and optimizing a lightweight mirror structure. Firstly, the initial designs are obtained combining global sensitivity factor mapping and local distribution optimization. Then, the optimal model is selected through multi-objective optimization and decision making. Subsequently, the FEA (finite element analysis) results indicate that, under the same mass, the proposed design exhibits better optomechanical performance. Finally, in practical applications, the approach presented in this paper outperforms the traditional design for each technological requirement, including a 62% reduction in RMS and a higher lightweight ratio. This method offers a kind of novel design and optimization process for space-based optomechanical lightweight structures.
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Psoriasis is accepted as a chronic, inflammatory, immune-mediated skin disease triggered by complex environmental and genetic factors. For a long time, disease recurrence, drug rejection, and high treatment costs have remained enormous challenges and burdens to patients and clinicians. Natural products with effective immunomodulatory and anti-inflammatory activities from medicinal plants have the potential to combat psoriasis and complications. Herein, an imiquimod (IMQ)-induced psoriasis-like dermatitis model is established in mice. The model mice are treated with 1% rutaecarpine (RUT) (external use) or the oral administration of RUT at different concentrations. Furthermore, high-throughput 16S rRNA gene sequencing is applied to analyze the changes in the diversity and composition of the gut microbiota. Based on the observation of mouse dorsal skin changes, RUT can protect against inflammation to improve psoriasis-like skin damage in mice. Additionally, RUT could suppress the expression levels of proinflammatory cytokines (IL-23, IL-17A, IL-22, IL-6, and IFN-α) within skin tissue samples. Concerning gut microbiota, we find obvious variations within the composition of gut microflora between IMQ-induced psoriasis mice and RUT-treated psoriasis mice. RUT effectively mediates the recovery of gut microbiota in mice induced by IMQ application. Psoriasis is linked to the production of several inflammatory cytokines and gut microbiome alterations. This research shows that RUT might restore gut microbiota homeostasis, reduce inflammatory cytokine production, and ameliorate psoriasis symptoms. In conclusion, the gut microbiota might be a therapeutic target or biomarker for psoriasis that aids in clinical diagnosis and therapy.
Subject(s)
Dermatitis , Gastrointestinal Microbiome , Indole Alkaloids , Psoriasis , Quinazolinones , Humans , Animals , Mice , Imiquimod/adverse effects , RNA, Ribosomal, 16S/genetics , Psoriasis/chemically induced , Psoriasis/drug therapy , Cytokines/metabolism , Disease Models, Animal , Mice, Inbred BALB CABSTRACT
PURPOSE: A meta-analysis study was performed to systematically assess the association between tea consumption and CRC risk. METHODS: Cochrane Library, Embase, PubMed, and Web of Science were retrieved to collect articles in English since 24 July 2023. Databases were searched and evaluated by two reviewers independently.We screened the literature based on inclusion and exclusion criteria. After determining the random effect model or fixed utility model based on a heterogeneity test, odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. RESULTS: We included fourteen articles in this meta-analysis. We analyzed the data using a random effect model to explore the association between tea consumption and CRC because of apparent heterogeneity (P < 0.001, I2 = 99.5%). The combined results of all tests showed that there is no statistically significant association between tea consumption and CRC risk (OR = 0.756, 95%CI = 0.470-1.215, P = 0.247). Subsequently, subgroup analysis and sensitivity analysis were performed. Excluding any single study, the overall results ranged from 0.73 (95%CI = 0.44-1.20) to 0.86 (95%CI = 0.53-1.40). It was determined that there was no significant publication bias between tea consumption and CRC risk (P = 0.064) by Egger's tests. CONCLUSIONS: The results indicated that tea consumption may not be significantly associated with the development of CRC. IMPLICATIONS OF KEY FINDINGS: Tea reduces colon cancer risk by 24%, but the estimate is uncertain. The actual effect on risk can range from a reduction of 51% to an increase of 18%, but regional and population differences may cause differences.
Subject(s)
Colonic Neoplasms , Research , Humans , Databases, Factual , Tea/adverse effectsABSTRACT
As space resources become increasingly constrained, the major space-faring nations are establishing large space target monitoring systems. There is a demand for both the number and the detection capability of space-based optical monitoring equipment. The detection range (i.e., field of view) and parasitic capability (lightweight and small size) of a single optical payload will largely reduce the scale and cost of the monitoring system. Therefore, in this paper, the optic-mechanical system of an ultra-lightweight and ultra-compact space camera and the optical alignment method are investigated around a fully freeform off-axis triple-reversal large field of view (FOV) optical system. The optic-mechanical system optimisation design is completed by adopting the optic-mechanical integration analysis method, and the weight of the whole camera is less than 10 kg. In addition, to address the mounting problems caused by the special characteristics of the freeform surface optical system, a dual CGH coreference alignment method is innovatively proposed. The feasibility of the method is verified by the mounting and testing test, and the test results show that the system wavefront difference is better than 1/10 λ. The imaging test of the space camera and the magnitude test results meet the design requirements of the optical system. The optic-mechanical system design method and alignment method proposed in this paper are instructive for the design and engineering of large field of view full freeform optical loads.
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The arbitrary disposal of used brake pads from motor vehicles has resulted in severe heavy metal pollution and resource wastage, highlighting the urgent need to explore the significant untapped potential of these discarded materials. In this study, The in-situ growth of highly dispersed Fe2O3 nanocrystals was achieved by simple oxidation annealing of brake pad debris(BPD). Interestingly, Cu remained unoxidized and acted as a "valence state transformation bridge of Fe2O3" to construct the "triple Fe-C-Cu sites". The Fenton degradation experiment of pollutants was conducted under constant temperature conditions at 40 °C, a stirring rate of 1300 rpm, a pH value of 3, a catalyst dosage of 0.5 g/L, pollutant dosage ranging from 50 to 400 mg/L, and H2O2 dosage of 0.25 g/L. Experimental results showed that BPD treated at 300 °C for 2 h exhibited optimal Fenton-like oxidation activity, achieving rapid degradation of over 90 % of refractory antibiotics, such as tetracycline and ciprofloxacin, in organic wastewater within 10 min. This remarkable performance was mainly attributed to the synergistic effect of "Fe-C-Cu triple sites", where the electron-donating role of C in the Fe-C and Cu-C interfaces facilitated the conversion of the Fe(III) to Fe(II) and Cu(II) to Cu(I). In addition, the ability of Cu2+ to accept electrons at the Fe-Cu interface promoted the transition from Fe (II) to Fe (III). This "balance of electron gain and loss" accelerated the interfacial electron transfer and the recycle of dual Fenton sites, Fe(II)/Fe(III) and Cu(I)/Cu(II), to generate more ·OH from H2O2. Therefore, this strategy of functionalizing BPD as Fenton-like catalysts without the addition of external Fe provides intriguing prospects for understanding the construction of Fe-based Fenton catalysts and resource utilization of Fe-containing solid waste materials.
Subject(s)
Environmental Pollutants , Iron , Iron/chemistry , Hydrogen Peroxide/chemistry , Automobiles , Oxidation-Reduction , Ferric Compounds/chemistry , Ferrous Compounds , CatalysisABSTRACT
To deal with the sideslip angle caused by the current disturbances or transverse motion for path following of under-actuated ships, a nonlinear observer established by an exponential function is introduced in the backstepping approach which converts the path following into heading control. Then, the model predictive control (MPC) method is used as a heading controller, addressing the rudder optimization. A linear extended state observer technology was exploited to estimate yaw rate, external disturbances, and internal uncertainties, which could avoid measuring the high-order state used in the MPC controller and promote the accuracy of the MPC internal model. Moreover, an inverse tangent function is applied to develop a new method for switching the reference heading angle to reduce rudder amplitude when the ship is choosing the next waypoint. Finally, the validity and reliability of the design method were verified through comparative computer simulation experiments.
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Objective: To analyze the risk factors of lower extremity deep venous thrombosis (DVT) detachment in orthopedic patients, and to establish a risk nomogram prediction model. Methods: The clinical data of 334 patients with orthopedic DVT admitted to the Third Hospital of Hebei Medical University from January 2020 to July 2021 were retrospectively analyzed. General statistics included gender, age, BMI, thrombus detachment, inferior vena cava filter window type, filter implantation time, medical history, trauma history, operation, use of tourniquet, thrombectomy, anesthesia mode, anesthesia grade, operative position, blood loss during operation, blood transfusion, immobilization, use of anticoagulants, thrombus side, thrombus range, D-dimer content before filter implantation and during removal of inferior vena cava filter. Logistic regression was used to perform univariate and multivariate analysis on the possible factors of thrombosis detachment, screen out independent risk factors, establish a risk nomogram prediction model by variables, and internally verify the predictability and accuracy of the model. Results: Binary logistic regression analysis showed that Short time window filter (OR = 5.401, 95% CI = 2.338-12.478), lower extremity operation (OR = 3.565, 95% CI = 1.553-8.184), use of tourniquet (OR = 3.871, 95% CI = 1.733-8.651), non-strict immobilization (OR = 3.207, 95% CI = 1.387-7.413), non-standardized anticoagulation (OR = 4.406, 95% CI = 1.868-10.390), distal deep vein thrombosis (OR = 2.212, 95% CI = 1.047-4.671) were independent risk factors for lower extremity DVT detachment in orthopedic patients (P < 0.05). Based on these six factors, a prediction model for the risk of lower extremity DVT detachment in orthopedic patients was established, and the risk prediction ability of the model was verified. The C-index of the nomogram model was 0.870 (95% CI: 0.822-0.919). The results indicate that the risk nomogram model has good accuracy in predicting the loss of deep venous thrombosis in orthopedic patients. Conclusion: The nomogram risk prediction model based on six clinical factors, including filter window type, operation condition, tourniquet use, braking condition, anticoagulation condition, and thrombosis range, has good predictive performance.
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We propose an interpretation of moiré phenomenon in the image domain. The interpretation is basically based on the analysis of the waveform of the line families. The period, angle, and intensity profile of moiré fringes can be obtained directly in the image domain according to this interpretation. Moreover, pseudo-moiré can be interpreted visually with the consideration of the illusional contrast of the human visual system. The interpretation, which is consistent with the Fourier theory when the two superposed gratings are periodic, involves only the image domain and shows remarkable simplicity, just like the indicial equation method.
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In this work, one-dimensional (1D) ZnFe2O4@carbon@MoS2/FeS2 composites were synthesized by hydrothermal method, magnetic-field-induced distillation-precipitation polymerization and high-temperature carbonization. The structure, morphology, composition, magnetic performance and electromagnetic (EM) wave absorbing properties of the composites were systematically studied. The composites show strong microwave absorption (MA) capacity with a minimum reflection loss (RLmin) value of -52.5 dB at 13.2 GHz, and have an effective absorption frequency range of 10.10-15.08 GHz with a bandwidth of 4.98 GHz when the thickness is 2.23 mm. It is expected that as-synthesized 1D ZnFe2O4@carbon@MoS2/FeS2 composites can be a promising EM wave absorption material.
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A flexural support technique for lightweighted Primary Mirror Assembly (PMA) of a space telescope is presented in this article. The proposed three-point flexural mount based on a cartwheel flexure can maintain the surface figure of the PMA in a horizontal optical testing layout. The on-orbit surface error of the PMA causes significant degradation in image quality. On-ground optical testing cannot determine the zero-gravity figure of the PMA due to surface distortion by gravity. We unveiled the crucial fact that through a delicate mounting structure design, the surface figure can remain constant precisely without inducing distinguishable astigmatism when PMA rotates with respect to the optical axis, and the figure can be considered as the zero-gravity surface figure on the orbit. A design case is described to show the lightweight design of a SiC mirror and the optimal flexural mounting. Topology optimization and integrated opto-mechanical analysis using the finite element method are utilized in the design process. The Primary Mirror and mounting structures were fabricated and assembled. After the PMA mirror surface was polished to λ/50 RMS, optical testing in different clocking configurations was performed, respectively, through rotating the PMA by multiple angles. Test results show that the surface figure remained invariant, indicating that gravity release on the orbit will not cause an additional surface error. Vibration tests including sweep sine and random vibration were also performed to validate the mechanical design. The requirements for the mounting technique in space were qualified.