Multi-Sensor Fault Diagnosis Based on Time Series in an Intelligent Mechanical System.

Intelligent mechanical systems are a focused area nowadays. One of the requirements of intelligent mechanical systems is to achieve intelligent fault diagnosis through the real-time acquisition and analysis of data from various sensors installed on mechanical components. In this paper, a new fault diagnosis method is proposed to solve the problems of difficulty in integrating the fault diagnosis algorithm and locating fault parts due to the complexity of modern mechanical systems. The complexity of modern industrial intelligent systems is due to the fact that the systems are composed of multiple components and there are various connections between them. Common fault diagnosis is to design specialized fault identification algorithms for the physical characteristics of each component, and the integration of different algorithms is a major challenge for system performance. Therefore, this paper investigates a general algorithm for the fault diagnosis of complex systems using the timing characteristics of sensors and transfer entropy. The fault diagnosis algorithm is based on the prediction of multi-dimensional long time series using Autoformer, and fault identification is performed based on the deviation of the predicted value from the actual value. After fault identification, a root cause analysis method of faults based on transfer entropy is proposed. The method can locate the component where the fault occurs more accurately based on the analysis of the cause-effect relationship of each component and help maintenance personnel to troubleshoot the fault.

Forecasting sensitive targets of the kynurenine pathway in pancreatic adenocarcinoma using mathematical modeling.

In this study, a new mathematical model was established and validated to forecast and define sensitive targets in the kynurenine pathway (Kynp) in pancreatic adenocarcinoma (PDAC). Using the Panc-1 cell line, genetic profiles of Kynp molecules were tested. qPCR data were implemented in the algorithm programming (fmincon and lsqnonlin function) to estimate 35 parameters of Kynp variables by Matlab 2017b. All tested parameters were defined as non-negative and bounded. Then, based on experimental data, the function of the fmincon equation was employed to estimate the approximate range of each parameter. These calculations were confirmed by qPCR and Western blot. The correlation coefficient (R) between model simulation and experimental data (72 hours, in intervals of 6 hours) of every variable was >0.988. The analysis of reliability and predictive accuracy depending on qPCR and Western blot data showed high predictive accuracy of the model; R was >0.988. Using the model calculations, kynurenine (x3, a6), GPR35 (x4, a8), NF-kßp105 (x7, a16), and NF-kßp65 (x8, a18) were recognized as sensitive targets in the Kynp. These predicted targets were confirmed by testing gene and protein expression responses. Therefore, this study provides new interdisciplinary evidence for Kynp-sensitive targets in the treatment of PDAC.

Intra-articular injection of hUC-MSCs expressing miR-140-5p induces cartilage self-repairing in the rat osteoarthritis.

INTRODUCTION: Currently, osteoarthritis (OA) receives global increasing attention because it associates severe joint pain and serious disability. Stem cells intra-articular injection therapy showed a potential therapeutic superiority to reduce OA development and to improve treating outputs. However, the long-term effect of stem cells intra-articular injection on the cartilage regeneration remains unclear. Recently, miR-140-5p was confirmed as a critical positive regulator in chondrogenesis. We hypothesized that hUC-MSCs overexpressing miR-140-5p have better therapeutic effect on osteoarthritis. MATERIALS AND METHODS: To enhance stem cell chondrogenic differentiation, we have transfected human umbilical cord mesenchymal stem cells (hUC-MSCs) with miR-140-5p mimics and miR-140-5p lentivirus to overexpress miR-140-5p in a short term or a long term accordingly. Thereafter, MSCs proliferation, chondrogenic genes expression and extracellular matrix were assessed. Destabilization of the medial meniscus (DMM) surgery was performed on the knee joints of SD rats as an OA model, and then intra-articular injection of hUC-MSCs or hUC-MSCs transfected with miR-140-5p lentivirus was carried to evaluate the cartilage healing effect with histological staining and OARSI scores. The localization of hUC-MSCs after intra-articular injection was further confirmed by immunohistochemical staining. RESULTS: Significant induction of chondrogenic differentiation in the miR-140-5p-hUC-MSCs (140-MSCs), while its proliferation was not influenced. Interestingly, intra-articular injection of 140-MSCs significantly enhanced articular cartilage self-repairing in comparison to normal hUC-MSCs. Moreover, we noticed that intra-articular injection of high 140-MSCs numbers reinforces cells assembling on the impaired cartilage surface and subsequently differentiated into chondrocytes. CONCLUSIONS: In conclusion, these results indicate therapeutic superiority of hUC-MSCs overexpressing miR-140-5p to treat OA using intra-articular injection.

Three-Dimensional Device-Free Localization for Vehicle.

Device-free localization (DFL) is a promising technique which could provide localization information for a target without requiring an electronic device. With the development of the smart city and smart transportation, DFL could form part of a basic technique that could be used to track and localize roadside vehicles. In this paper, some algorithms for three-dimensional (3D) DFL for vehicle surveillance are developed, including statistical methods for data, a method for communication link selection, a novel method of communication link weight allocation and some other minor approaches to obtain the location and approximate size of a static vehicle, as a basic technique of moving vehicle detection. Then, an experimental system is designed. Through security monitoring wireless sensor networks (WSN), real-time vehicle characteristics (i.e., location and size) are calculated automatically and intuitively displayed through a heat map. Experiments are performed to validate the effect of the proposal and the accuracy of the localization and size estimation.

Clinical Study of Ankle Fracture Combined With Deltoid Ligament Injury: Repair or Not? A Retrospective, Comparative Study.

This study retrospectively evaluated patients with ankle fracture to compare the prognosis between patients who had primary repair of the superficial deltoid ligament and those who did not. A total of 71 patients with ankle fracture and fracture-dislocation combined with deltoid ligament injury were divided into 2 groups: repair of superficial layer group (33 cases) and nonrepair group (38 cases). For the repair group, patients first underwent open reduction and internal fixation of the lateral malleolus and received a stress test. If the syndesmosis was widened, it would undergo fixation of the syndesmosis with screws. If instability of the ankle joint was observed, patients might further undergo repair of the superficial deltoid ligament. Ultimately, postoperative functions were evaluated using the Philips and Schwartz scale. All patients achieved bony union without significant pain. In the repair group, plantar and dorsi flexions were 2.5 ± 4.2° (range 0 to 10) and 7 ± 7.1° (range 0 to 20) less than the normal side, respectively. In the nonrepair group, the plantar and dorsi flexions were 2.8 ± 4.6° (range 0 to 10) and 6.6 ± 5.9° (range 0 to 20) less than the normal side. Meanwhile, the Philips and Schwartz scores of the repair and nonrepair groups were 92.5 ± 4.4 (range 80 to 100) and 93.4 ± 3.8 (range 85 to 100), respectively. But the difference of prognosis between the 2 groups was not statistically significant. In conclusion, for ankle joint fracture combined with deltoid ligament injury, routinely exploring or repairing the deltoid ligament was not recommended, but repair of the deltoid ligament increased stability of the ankle joint in the early postoperative stage.

A classification and grading system for Barton fractures.

PURPOSE: We described a morphological classification and grading system for volar Barton fractures. METHODS: We divided these fractures into four types: typical Barton, ulna Barton, radial Barton, comminuted Barton. Moreover, we graded the fractures into two degrees: simple split and split-depression. We retrospectively reviewed all wrist radiographs showing Barton fractures in our hospital between January 2013 and January 2015. We identified 100 cases whose records and radiographs were reviewed and included 36 men and 64 women with a mean age of 50 years (15-78). The morphological classification was applied to the 100 cases by three reviewers on two occasions using the Kappa statistic. RESULTS: The inter- and intra-observer reliability of the morphological classification was 0.71-0.80 and 0.68-0.88, respectively. The distribution of typical, ulna, radial and comminuted Barton type fractures was 69 %, 7 %, 5 % and 19 %, respectively. Grade 2 fractures accounted for 49 % in our series. CONCLUSIONS: This classification and grading system of Barton fractures is likely to have implications in terms of pathophysiology and surgical technique.

Hyaluronan tetrasaccharide exerts neuroprotective effect and promotes functional recovery after acute spinal cord injury in rats.

The objective of this study was to explore the therapeutic efficiency of hyaluronan tetrasaccharide (HA4) treatment after spinal cord injury (SCI) in rats and to investigate the underlying mechanism. Locomotor functional and electrophysiological evaluations revealed that the behavioral function of rats in the HA4-treated group was significantly improved compared with the vehicle-treated group. The expression of brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor (VEGF), cluster determinant (CD44) and Toll-like receptor-4 (TLR-4) was obviously upregulated in the HA4-treated group than that in the sham and vehicle-treated group. Furthermore, HA4 could induce BDNF and VEGF expression in the astrocytes in vitro. In addition, the high expression of BDNF and VEGF could be inhibited by blocking CD44 and TLR-4. These findings indicate that HA4 could be useful as a promising therapeutic agent for SCI and might exert the effect by interaction with the CD44 and TLR-4.

Is minimally invasive plating osteosynthesis for humeral shaft fracture advantageous compared with the conventional open technique?

BACKGROUND: The minimally invasive plate osteosynthesis (MIPO) technique has been described and used effectively in humeral shaft fractures. However, the postoperative deformity resulting from malreduction with the minimally invasive technique has not received adequate attention. The purpose of this study was to evaluate the postoperative malrotation and the functional results of the MIPO technique and conventional plating in open reduction and internal fixation after humeral shaft fracture. METHODS: A prospective cohort research was performed; 53 cases of humeral shaft fractures in a level I trauma center were included and allocated into group I for open reduction and internal fixation or group II for MIPO. Computed tomography was used to measure the postoperative malrotation. The status of the union, functional scoring, and muscle strength were recorded at 12 months after surgery. RESULTS: Both groups exhibited satisfactory union results and final shoulder function scoring. Shoulder girdle musculature of both groups exhibited considerable strength loss with no obvious intergroup discrepancy, with greater internal rotation strength loss compared with external rotation. A significantly increased incidence of postoperative malrotation >20° was observed in the MIPO group (40.9% vs. 0%; P < .01). A linear correlation between postoperative malrotation and range of rotation loss was observed. CONCLUSIONS: The MIPO technique might be advantageous as a cosmetic consideration; however, it did not improve postoperative function and strength restoration results more than the open technique. Moreover, MIPO was associated with greater postoperative malrotation, which was considered to be correlated with subsequent long-term shoulder degeneration.

The risk factors of perioperative hemoglobin and hematocrit drop after intramedullary nailing treatment for intertrochanteric fracture patients.

BACKGROUND: The objective of this study was to analyze the risk factors associated with the hemoglobin and hematocrit drops in the early postoperative period for intertrochanteric fracture patients with intramedullary nailing treatment. METHODS: From January 2003 to December 2013, 634 intertrochanteric fracture patients with complete information were recruited into the study. Their age, gender, operating time, medical diseases, blood routine examination at admission and postoperative first day, and the days between the trauma and operation were recorded. RESULTS: The hemoglobin (HGB) change of patients (<75 years) was significantly greater than that of patients (>75 years) (P = 0.039). Meanwhile, the change of hematocrit (HCT) level of patients (<75 years) was greater than that of patients (>75 years), but the difference was not significant (P = 0.062). The gender had no significant influence on HCT and HGB. The HGB and HCT change of patients with diabetes (ΔHCT, 8.47 ± 3.36 %; ΔHGB, 29.19 ± 13.10 g/l) were statistically greater than that of patients without diabetes (ΔHCT, 5.52 ± 3.84 %; ΔHGB, 19.81 ± 14.68 g/l) (P = 0.006, P = 0.022). The hypertension and coronary heart disease had no significant influence on the change of HCT and HGB levels. The operation time had a significant influence on the change of HCT and HGB. The ΔHCT and ΔHGB in the group for which the time was more than 48 h between the trauma and operation were greater than that in the group with less than 48 h between the trauma and operation but not significantly different (ΔHCT, P = 0.672; ΔHGB, P = 0.66). CONCLUSION: The factors of age, medical disease such as diabetes, operation time, and time between the trauma and operation may be associated with the change of perioperative hemoglobin and hematocrit levels for intertrochanteric fracture patients after intramedullary nailing treatment in the early postoperative period.

[A comparative research on the treatment of ankle fracture with dislocation between emergency surgery and selective surgery].

OBJECTIVE: To investigate the differences between emergency surgery and selective surgery treatment of ankle fractures with dislocation. METHODS: In the study, 40 patients with ankle fracture and dislocation were treated and followed up from May 2013 to May 2014, and all the data were collected and analyzed. The subjects involved 29 male patients and 11 female patients. The patients were randomly separated into two groups, and the patients in group A were given surgical intervention within 6 hours after injury, while those in group B were initially given close reduction and given selective operation when the soft tissue condition got better. Group A contained 13 male patients and 7 female patients with average age of 37.10; Group B consisted of 15 male and 5 female, with average age of 37.85. RESULTS: The Baird-Jackson score was applied for assessment of the patients' outcomes. According to the score, the outcomes were classified into excellent, good, fair, and poor. In group A (emergency group), the outcomes were 13 (65.0%), 4 (20.0%), 3 (15.0%), and 0, respectively. In group B (selective group), they were 11 (55.0%), 7 (35.0%), 2 (10.0%), and 0, respectively. The numbers of the patients from excellent to poor were 24 (55.0%), 11 (27.5%), 5 (12.5%), and 0, respectively. CONCLUSION: There is no significant difference in postoperative function between the two groups, however, early surgical intervention can benefit in accomplishing anatomical reduction much easier and shortening the time of hospitalization, which is cost-saving for the patients.

[Study of a preoperative deep venous thrombosis predictor score for patients with fresh lower extremity fractures].

OBJECTIVE: To establish a preoperative deep venous thrombosis predictor score for patients with fresh lower extremity fractures by statistical analysis. METHODS: From January 2011 to December 2012, 1 705 patients with fresh lower extremity fractures were admitted to department of orthopaedic trauma, Beijing Jishuitan Hospital. They were randomly divided into two groups, the group 1 (n = 879) was used to screen risk factors and derived a predictive models based on logistic regression, the group 2 (n = 826) validated the models. RESULTS: Among the patients, there were 1 106 male and 599 female patients, with an average age of (50 ± 18) years.Variables related to preoperative deep venous thrombosis were age, length of time before surgery, cause of injury, low/high-energy injury, location of injury, history of cardiovascular and cerebrovascular diseases, and D-Dimer. The scores based on OR were: age ≤ 35 years: 1 point, > 35- < 65 years: 4 points, ≥ 65 years: 6 points; length of time before surgery, < 8 days:1 point, ≥ 8 days:2 points;low-energy injury:1 point, high energy injury:3 points;location of injury, foot and ankle:1 point, calf:3 points, around the knee: 5 points, femoral diaphysis and proximal femur:7 points, pelvis and acetabulum:4 points, ≥ 2 sites:6 point;history of cardiovascular and cerebrovascular diseases, yes:2 points, no:1 point. D-Dimer < 600 µg/L:1 point, ≥ 600 µg/L:3 points. Area under receiver operating characteristic curve was 0.79, critical point 15.5 points, sensitivity was 77.00%, specificity was 68.17%. CONCLUSION: The score can predict the preoperative deep venous thrombosis for patients with fresh lower extremity fractures, but limited.

[Tibiotalar or tibiocalcaneal arthrodesis using the ilizarov technique in the presence of infected nonunions of ankle joints].

OBJECTIVE: To evaluate the results of managing the infected nonunions of distal tibial fractures combined with talar fracture and calcaneal fracture with tibial bone transport, tibiotalar or tibiocalcaneal arthrodesis using the hybrid external fixator. METHODS: A retrospective review of 26 patients who underwent either tibiotalar arthodesis or tibiocalcaneal arthodesis using an hybrid external fixator for infected nonunions of distal tibial fractures, talar and calcaneal fractures after tibial bone distraction was made. Each patient had a debridement of all infected and nonviable bones, the wound area were 2 cm×4 cm-4 cm×8 cm. The bony surfaces of distal tibia and talus were prepared for the fusion followed by application of an Orthofix's hybrid external fixator. RESULTS: The remaining 18 patients undertook debridement at the docking sites, and 14 of them had autogenous bone grafting. There was a mean follow-up of 32 months (22-38 months). All the patients had successful fusions. There were no recurrent deep infections or amputations. Two patients had 6° of varus deformity at the docking site. CONCLUSION: Tibiotalar or tibiocalcaneal arthrodesis using the Ilizarov technique is viable alternative to amputation in patients with infected nonunions,especially if there is a large bone loss of the tibias, talus and calcaneus.

The distinct prediction standards for radiological assessments associated with soft tissue injuries in the acute tibial plateau fracture.

The goal of this study was to assess the incidence of soft tissue injury in the tibial plateau fracture by magnetic resonance image (MRI) and reveal the relationship between the articular widening/depression and the risk of meniscus and ligament disorder. A total of 54 patients with tibial plateau fracture were indicated for operative intervention. Soft tissue injuries were assessed by MRI. Meniscus, anterior/posterior cruciate ligaments and medial/lateral collateral ligaments injuries on MRI were evaluated. The articular widening/depression was measured in picture archiving and communication systems. Schatzker classification of fracture types was not significantly associated with soft tissue injuries. The rates of soft tissue injury in types IV and II (respectively, 85.7 and 74.1 %) were higher than those in other types. The meniscus injury was the most common soft tissue damage, and the incidence of meniscus injury was 55.6 %. When LPDCT and LPWCT were, respectively, about 7.6 mm and 10.1 mm and LPDX-ray and LPWX-ray, respectively, 5.6 and 7.4 mm, more attention should be paid on the collateral and cruciate ligament injuries in types I, II and III. Furthermore, when LPWCT and LPWX-ray were, respectively, about 10.3 and 8.6 mm, the collateral and cruciate ligaments were susceptible to injury in types IV and V. In conclusion, tibial plateau fracture can occur high morbidity of soft tissue injury, including meniscus and ligament disorder. X-ray and CT scan had different predicting standards for soft tissue injury, and the articular widening/depression in the tibial plateau was associated with meniscus and ligament injuries.

The "lateral gutter drive-through" sign revisited: a cadaveric study exploring its real mechanism based on the individual posterolateral structure of knee joints.

BACKGROUND: Although the validity of the "lateral gutter drive-through" (LGDT) test has been proved to offer high sensitivity and specificity in diagnosing the posterolateral rotational instability of knee joints, the real mechanism on how the injury pattern of individual posterolateral knee structure triggers the positive LGDT sign still remains unknown. HYPOTHESIS: A certain amount of popliteus tendon (POP-T) laxity resulted from specific injury patterns of individual posterolateral knee structure or some degree of medial structural injury will lead to positive LGDT sign. STUDY DESIGN: Controlled laboratory study. METHODS: Seven non-paired intact cadaveric knees were divided into four groups and tested under unique sequential sectioning sequences including: (1) distal POP-T and popliteofibular ligament (PFL) (n = 2); (2) PFL and distal POP-T (n = 3); (3) lateral collateral ligament (LCL), distal POP-T and PFL (n = 1); (4) superficial medial collateral ligament (sMCL), deep MCL, posterior oblique ligament (POL), anterior cruciate ligament (ACL) and posterior cruciate ligament (PCL) (n = 1). The LGDT tests and the measurements of external tibial rotational angle (ETRA) were first performed on all the intact knees and then at each time point when an additional structure was sectioned. Results of each LGDT test and the absolute value of increased ETRA compared with the intact knee were recorded. Each knee was tested at 30° of flexion. A navigation system was used to measure motion changes of the tibia with respect to the femur. RESULTS: Initially, the LGDT tests all showed negative on each of the intact knee. Isolated sectioning of the distal POP-T, PFL or the LCL produced increased but insignificant ETRA with the LGDT tests still negative. However, simultaneous sectioning of the distal POP-T and PFL produced significantly increased ETRA with the LGDT tests changed to positive. In addition, for the knee with medial structural injuries, the LGDT test could also be positive only when the posteromedial structures (sMCL, deep MCL, POL) and the cruciate ligaments (ACL and PCL) were all sectioned. CONCLUSION: In this cadaveric sequential sectioning study, the LGDT test showed positive merely at the following two situations: (1) the distal POP-T and PFL were both sectioned; (2) the posteromedial structures (sMCL, deep MCL and POL) and the cruciate ligaments (ACL and PCL) were all sectioned. CLINICAL RELEVANCE: Accuracy of the LGDT test in diagnosing acute or chronic posterolateral corner (PLC) injuries will improve with the information in this study. It was the combined POP-T and PFL injuries that finally led to a positive LGDT sign. However, one should be cautious to use the LGDT test in diagnosing the PLC injuries when posteromedial structures and cruciate ligaments were all involved.

Delayed ORIF of proximal humerus fractures at a minimum of 3 weeks from injury: a functional outcome study.

PURPOSE: To evaluate the clinical results of open reduction and internal fixation (ORIF) in proximal humerus fractures with delayed presentation. DESIGN: Retrospective comparative study. SETTING: Level III. METHODS: From June 2005 to June 2010, thirty-nine (39) proximal humerus fractures were treated with ORIF after a delay of 21-120 days from the initial injury. Patients were divided into three groups: (1) isolated 2-part greater tuberosity fractures; (2) part surgical neck fractures; and (3) 3- and 4-part complex fractures. The range of motion (ROM), visual analogue scale (VAS), Constant-Murley score, University of California Los Angeles (UCLA) scoring system score and Simple Shoulder Test (SST) score were all recorded. The results were analyzed with the use of the Mann-Whitney U test and stratified by age, gender, side of injury, interval from injury to surgery, and postoperative functional results. Additionally, the results of different fracture types and complications were compared across the three groups. RESULTS: The mean forward flexion was 143.8°±28.9°, external rotation was 33.2°±19.6°, and internal rotation was up to the T10 level. The mean VAS was 0.8±1.2; the mean Constant score was 82.0±15.0; the UCLA score was 27.2±7.1; and the mean SST was 9.5±2.0 at the last follow-up. There were no significant differences among the three groups except in internal rotation. Compared to those without any complications, patients with complications demonstrated worse ROM and a lower functional score (p<0.05). CONCLUSIONS: Delayed treatment of proximal humerus fractures is a challenging problem. With appropriate surgical technique, satisfactory results can be expected with respect to different fracture types, and complications may be avoided regardless of delay. LEVEL OF EVIDENCE: Therapeutic Level IV.

An effective method for small objects detection based on MDFFAM and LKSPP.

Object detection is one of the research hotspots in computer vision. However, most existing object detectors struggle with the identification of small targets. Therefore, the paper proposes two modules: the MDFFAM (Multi-Directional Feature Fusion Attention Mechanism) and the LKSPP (Large Kernel Spatial Pyramid Pooling), to enhance the detector's effectiveness in identifying subtle faults on the surface of mechanical equipment. LKSPP aims to expand the receptive field to capture high-level semantic features through large kernels. Meanwhile, the MDFFAM allows the network to efficiently utilize spatial location information and adaptively recognize detection priorities. In the detection task, MDFFAM effectively captures feature information in three spatial directions: width, height, and channel, with the location information fully utilized to establish stable long-range dependencies. Moreover, LKSPP boasts a larger receptive field and imposes less computational burden compared to the SPPCSPC by YOLOv7. Finally, experiments demonstrate that the proposed module effectively improves the detection accuracy for small targets, surpassing the state-of-the-art object detector, YOLOv7. Remarkably, MDFFAM incurs almost negligible computational overhead.

Arthroscopy-Assisted Closed Reduction and Percutaneous Internal Fixation for Medial Malleolus Fracture.

BACKGROUND: Arthroscopy-assisted closed reduction and percutaneous internal fixation is a minimally invasive technique for medial malleolus fracture treatment. The purpose of the study was to assess the quality and functional outcomes of this technique. METHODS: Seventy-eight patients with combined medial malleolus fractures were treated with arthroscopy-assisted closed reduction and percutaneous screw fixation technique. The surgical procedure was described in detail; the clinical efficacy of this method was evaluated in terms of time of operation, postoperative complications, and fracture healing time; and functional outcomes were analyzed. RESULTS: All of the patients were followed up for a minimum of 12 months without complications of the medial malleolus wound, and all of the medial malleolus fractures healed within 6 to 8 weeks. At the last follow-up, the visual analog scale scores ranged from 0 to 3 and the American Orthopaedic Foot and Ankle Society ankle and hindfoot function scores ranged from 75 to 95. CONCLUSIONS: Arthroscopy-assisted closed reduction and percutaneous internal fixation makes the treatment of medial malleolus fractures less invasive compared with traditional surgical methods and allows simultaneous exploration and management of the articular surface.

Effects of 2,4,6-Trichloroanisole on the morphological development and motility of zebrafish.

2,4,6-Trichloroanisole (2,4,6-TCA), a compound with a characteristic earthy odor, is a common source of odorous pollutants in drinking water and wine. However, research on its biological toxicity is limited. In this study, we used zebrafish as an indicator model to investigate the effects of 2,4,6-TCA exposure on morphological development, oxidative stress, apoptosis, heart rate, blood flow, and motility. We found that exposure to 2,4,6-TCA resulted in significant spinal, tail, and cardiac deformities in zebrafish larvae and promoted a pronounced oxidative stress response and extensive cell apoptosis, notably in the digestive tract, head, spine, and heart, ultimately leading to significant reductions in zebrafish heart rate, blood flow, and motility. Moreover, these effects became more pronounced with an increase in the concentration of 2,4,6-TCA to which the zebrafish were exposed. Furthermore, qPCR analysis revealed that exposure to 2,4,6-TCA promoted significant changes in the expression levels of genes associated with oxidative stress, apoptosis, cardiac development, and the nervous system, particularly key genes (p53, apaf1, casp9, and casp3) in the mitochondrial apoptotic pathway, which were significantly upregulated. Similarly, we detected significant upregulation of ache gene expression. These findings indicated that exposure to 2,4,6-TCA resulted in the accumulation of reactive oxygen species in zebrafish, induced strong oxidative stress responses, and triggered lipid peroxidation and extensive cell apoptosis. Cellular apoptosis, which mitochondrial signaling pathways may mediate, has been found to lead to malformations in zebrafish embryos, resulting in significant reductions in cardiac function and motility. To our knowledge, this is the first systematic assessment of the toxicity of 2,4,6-TCA, and our findings provide an important reference for risk assessment and early warning of 2,4,6-TCA exposure.

A Genomewide Evolution-Based CRISPR/Cas9 with Donor-Free (GEbCD) for Developing Robust and Productive Industrial Yeast.

Developing more robust and productive industrial yeast is crucial for high-efficiency biomanufacturing. However, the challenges posed by the long time required and the low abundance of mutations generated through genomewide evolutionary engineering hinder the development and optimization of desired hosts for industrial applications. To address these issues, we present a novel solution called the Genomewide Evolution-based CRISPR/Cas with Donor-free (GEbCD) system, in which nonhomologous-end-joining (NHEJ) repair can accelerate the acquisition of highly abundant yeast mutants. Together with modified rad52 of the DNA double-strand break repair in Saccharomyces cerevisiae, a hypermutation host was obtained with a 400-fold enhanced mutation ability. Under multiple environmental stresses the system could rapidly generate millions of mutants in a few rounds of iterative evolution. Using high-throughput screening, an industrial S. cerevisiae SISc-Δrad52-G4-72 (G4-72) was obtained that is strongly robust and has higher productivity. G4-72 grew stably and produced ethanol efficiently in multiple-stress environments, e.g. high temperature and high osmosis. In a pilot-scale fermentation with G4-72, the fermentation temperature was elevated by 8 °C and ethanol production was increased by 6.9% under the multiple stresses posed by the industrial fermentation substrate. Overall, the GEbCD system presents a powerful tool to rapidly generate abundant mutants and desired hosts, and offers a novel strategy for optimizing microbial chassis with regard to demands posed in industrial applications.

Effects of an explain-simulate-practice-communicate-support intervention on quality of life for patients with chronic heart failure: A randomized control trial.

Background: Patients with New York Heart Association (NYHA) grade III chronic heart failure (CHF) present with low capacity for daily activities, severe self-perceived burden, and poor quality of life. Effective nursing interventions may reduce patients' self-perceived burden and improve their quality of life. Objectives: To explore the effects of an explain-simulate-practice-communicate-support intervention on the self-perceived burden, cardiac function, and activities of daily living (ADL) ability in patients with New York Heart Association grade III chronic heart failure. Methods: Of the 100 patients with New York Heart Association grade III chronic heart failure who were electronically randomized and equally divided into control and intervention groups, data from 88 patients who completed our study were analyzed. The primary outcome was quality of life; secondary outcomes were self-perceived burden, 6-min walking test distances, serum N-terminal pro-brain natriuretic peptide levels, New York Heart Association cardiac function classification, and ability to perform activities of daily living. Results: After 12 weeks' intervention, the intervention group had significantly lower self-perceived burden, Minnesota Living with Heart Failure Questionnaire scores, N-terminal pro-brain natriuretic peptide levels, and New York Heart Association grades compared with the control group, while 6-min walking test distances, left ventricular ejection fraction, and modified Barthel Index scale scores were significantly higher than those in the control group (P > 0.05). Conclusions: The explain-simulate-practice-communicate-support intervention improved patients' quality of life through reducing the level of self-perceived burden, and improving cardiac function and activities of daily living ability. This intervention was found to be effective for patients with New York Heart Association grade III chronic heart failure.