Optimization of polydimethylsiloxane (PDMS) surface chemical modification and formulation for improved T cell activation and expansion.

Adoptive T cell therapy has undergone remarkable advancements in recent decades; nevertheless, the rapid and effective ex vivo expansion of tumor-reactive T cells remains a formidable challenge, limiting their clinical application. Artificial antigen-presenting substrates represent a promising avenue for enhancing the efficiency of adoptive immunotherapy and fostering T cell expansion. These substrates offer significant potential by providing flexibility and modularity in the design of tailored stimulatory environments. Polydimethylsiloxane (PDMS) silicone elastomer stands as a widely utilized biomaterial for exploring the varying sensitivity of T cell activation to substrate properties. This paper explores the optimization of PDMS surface modification and formulation to create customized stimulatory surfaces with the goal of enhancing T cell expansion. By employing soft PDMS elastomer functionalized through silanization and activating agent, coupled with site-directed protein immobilization techniques, a novel T cell stimulatory platform is introduced, facilitating T cell activation and proliferation. Notably, our findings underscore that softer modified elastomers (Young' modulus E∼300 kPa) exhibit superior efficacy in stimulating and activating mouse CD4+ T cells compared to their stiffer counterparts (E∼3 MPa). Furthermore, softened modified PDMS substrates demonstrate enhanced capabilities in T cell expansion and Th1 differentiation, offering promising insights for the advancement of T cell-based immunotherapy.

A Transportable Atomic Gravimeter with Constraint-Structured Active Vibration Isolation.

Many efforts have been taken in recent years to push atomic gravimeters toward practical applications. We demonstrate an atomic gravimeter named NIM-AGRb2 that is transportable and suitable for high-precision gravity measurements. Constraint-structured active vibration isolation (CS-AVI) is used to reduce the ground vibration noise. The constraint structure in CS-AVI ensures that the isolation platform only has vertical translation, with all other degrees of freedom (DoFs) being constrained. Therefore, the stability of active vibration isolation is enhanced. With the implementation of CS-AVI, the sensitivity of NIM-AGRb2 reached as low as 20.5 µGal/Hz1/2. The short-term sensitivity could be further reduced to 10.8 µGal/Hz1/2 in a seismologic observation station. Moreover, we evaluated the system noise of the gravimeter, and the results were consistent with our observations.

A discrete-event simulation model for assessing operating room efficiency of thoracic, gastrointestinal, and orthopedic surgeries.

BACKGROUND: In hospital management, pinpointing steps that most enhance operating room (OR) throughput is challenging. While prior literature has utilized discrete event simulation (DES) to study specific strategies such as scheduling and resource allocation, our study examines an earlier planning phase, assessing all workflow stages to determine the most impactful steps for subsequent strategy development. METHODS: DES models real-world systems by simulating sequential events. We constructed a DES model for thoracic, gastrointestinal, and orthopedic surgeries summarized from a tertiary Chinese hospital. The model covers preoperative preparations, OR occupation, and OR preparation. Parameters were sourced from patient data and staff experience. Model outcome is OR throughput. Post-validation, scenario analyses were conducted for each department, including: (1) improving preoperative patient preparation time; (2) increasing PACU beds; (3) improving OR preparation time; (4) use of new equipment to reduce the operative time of a selected surgery type; three levels of improvement (slight, moderate, large) were investigated. RESULTS: The first three improvement scenarios resulted in a 1%-5% increase in OR throughput across the three departments. Large reductions in operative time of the selected surgery types led to approximately 12%, 33%, and 38% increases in gastrointestinal, thoracic, and orthopedic surgery throughput, respectively. Moderate reductions resulted in 6%-17% increases in throughput and slight reductions of 1%-7%. CONCLUSIONS: The model could reliably reflect OR workflows of the three departments. Among the options investigated, model simulations suggest that improving OR preparation time and operative time are the most effective.

Surface chemical modification of poly(dimethylsiloxane) for stabilizing antibody immobilization and T cell cultures.

Advances in cell immunotherapy underscore the need for effective methods to produce large populations of effector T cells, driving growing interest in T-cell bioprocessing and immunoengineering. Research suggests that T cells demonstrate enhanced expansion and differentiation on soft matrices in contrast to rigid ones. Nevertheless, the influence of antibody conjugation chemistry on these processes remains largely unexplored. In this study, we examined the effect of antibody conjugation chemistry on T cell activation, expansion and differentiation using a soft and biocompatible polydimethylsiloxane (PDMS) platform. We rigorously evaluated three distinct immobilization methods, beginning with the use of amino-silane (PDMS-NH2-Ab), followed by glutaraldehyde (PDMS-CHO-Ab) or succinic acid anhydride (PDMS-COOH-Ab) activation, in addition to the conventional physical adsorption (PDMS-Ab). By employing both stable amide bonds and reducible Schiff bases, antibody conjugation significantly enhanced antibody loading and density compared to physical adsorption. Furthermore, we discovered that the PDMS-COOH-Ab surface significantly promoted IL-2 secretion, CD69 expression, and T cell expansion compared to the other groups. Moreover, we observed that both PDMS-COOH-Ab and PDMS-NH2-Ab surfaces exhibited a tendency to induce the differentiation of naïve CD4+ T cells into Th1 cells, whereas the PDMS-Ab surface elicited a Th2-biased immunological response. These findings highlight the importance of antibody conjugation chemistry in the design and development of T cell culture biomaterials. They also indicate that PDMS holds promise as a material for constructing culture platforms to modulate T cell activation, proliferation, and differentiation.

Metformin protects ovarian granulosa cells in chemotherapy-induced premature ovarian failure mice through AMPK/PPAR-γ/SIRT1 pathway.

Premature ovarian failure (POF) caused by chemotherapy is a growing concern for female reproductive health. The use of metformin (MET), which has anti-oxidative and anti-inflammatory effects, in the treatment of POF damaged by chemotherapy drugs remains unclear. In this study, we investigated the impact of MET on POF caused by cyclophosphamide (CTX) combined with busulfan (BUS) and M1 macrophages using POF model mice and primary granule cells (GCs). Our findings demonstrate that intragastric administration of MET ameliorates ovarian damage and alleviates hormonal disruption in chemotherapy-induced POF mice. This effect is achieved through the reduction of inflammatory and oxidative stress-related harm. Additionally, MET significantly relieves abnormal inflammatory response, ROS accumulation, and senescence in primary GCs co-cultured with M1 macrophages. We also observed that this protective role of MET is closely associated with the AMPK/PPAR-γ/SIRT1 pathway in cell models. In conclusion, our results suggest that MET can protect against chemotherapy-induced ovarian injury by inducing the expression of the AMPK pathway while reducing oxidative damage and inflammation.

Optimizing the management of electrophysiology labs in Chinese hospitals using a discrete event simulation tool.

BACKGROUND: The growing demand for electrophysiology (EP) treatment in China presents a challenge for current EP care delivery systems. This study constructed a discrete event simulation (DES) model of an inpatient EP care delivery process, simulating a generalized inpatient journey of EP patients from admission to discharge in the cardiology department of a tertiary hospital in China. The model shows how many more patients the system can serve under different resource constraints by optimizing various phases of the care delivery process. METHODS: Model inputs were based on and validated using real-world data, simulating the scheduling of limited resources among competing demands from different patient types. The patient stay consists of three stages, namely: the pre-operative stay, the EP procedure, and the post-operative stay. The model outcome was the total number of discharges during the simulation period. The scenario analysis presented in this paper covers two capacity-limiting scenarios (CLS): (1) fully occupied ward beds and (2) fully occupied electrophysiology laboratories (EP labs). Within each CLS, we investigated potential throughput when the length of stay or operative time was reduced by 10%, 20%, and 30%. The reductions were applied to patients with atrial fibrillation, the most common indication accounting for almost 30% of patients. RESULTS: Model validation showed simulation results approximated actual data (137.2 discharges calculated vs. 137 observed). With fully occupied wards, reducing pre- and/or post-operative stay time resulted in a 1-7% increased throughput. With fully occupied EP labs, reduced operative time increased throughput by 3-12%. CONCLUSIONS: Model validation and scenario analyses demonstrated that the DES model reliably reflects the EP care delivery process. Simulations identified which phases of the process should be optimized under different resource constraints, and the expected increases in patients served.

One-year direct and indirect costs of ischaemic stroke in China.

BACKGROUND: This is the first real-world study to estimate the direct costs and indirect costs of first-ever ischaemic stroke with 1-year follow-up in China, based on a nationally representative sample. METHODS: Patients were chosen from 20 geographically diverse sites from the nationally representative database China National Stroke Registry-III (CNSR-III). The inclusion criteria were surviving patients who were hospitalised with first-ever ischaemic stroke from February 2017 to February 2018 (the index event); aged 18-80 during the index event; no history of other stroke types. The primary endpoints were direct medical costs, direct non-medical costs, indirect costs and total cost (ie, the sum of all cost components). Patient characteristics and clinical data were extracted from CNSR-III. Stroke-related in-hospital direct medical costs were collected from hospital electronic medical records. The patient survey collected data related to out-of-hospital direct medical costs, direct non-medical costs and indirect costs. The secondary objective was to explore clinical factors associated with cost outcomes through univariate analysis and multiple regression. RESULTS: The study enrolled 520 patients. The total cost was 57 567.48 CNY, with 26 612.67 CNY direct medical costs, 2 787.56 CNY direct non-medical costs and 28 167.25 CNY indirect costs. Univariate analysis showed that longer lengths of stay during the index event, higher National Institutes of Health Stroke Scale (NIHSS) and modified Rankin Scale scores were associated with higher costs in all categories. Conversely, EuroQol 5 Dimension utility scores were associated with decreased costs except direct non-medical costs. Multiple regressions showed that higher admission NIHSS scores were independently associated with higher direct medical costs, indirect costs and total cost. Higher 3-month utilities were associated with lower total cost. CONCLUSION: This real-world study showed substantial 1-year economic burden following first-ever ischaemic stroke in China, and that indirect costs are a non-negligible driver of costs.

Inhibit ALDH3A2 reduce ovarian cancer cells survival via elevating ferroptosis sensitivity.

Ovarian cancer (OC) is a malignant gynecologic tumor with high morbidity and mortality. As a newly discovered mode of programmed cell death, ferroptosis has been involved in various pathological processes of kinds of tumors in recent years. Aldehyde dehydrogenase 3 family member A2 (ALDH3A2) catalyzes the oxidation of long-chain aliphatic aldehydes to fatty acid. ALDH3A2 has been shown to be associated with ferroptosis in acute myeloid leukemia (AML), but the mechanism remains unclear. In this study, we analyzed the TCGA and GTEx databases and showed that high ALDH3A2 expression predicted poor prognosis in ovarian cancer. Further studies found that knockout or overexpression of ALDH3A2 correspondingly increased or attenuated the ferroptosis sensitivity of ovarian cancer cells. And sequencing revealed that ALDH3A2 knockout led to the activation of lipid metabolic, GSH metabolic, phospholipid metabolic, and aldehyde metabolic pathways, suggesting that ALDH3A2 induced changes in the sensitivity of ovarian cancer cells to ferroptosis by affecting these metabolic processes. Our results provide a new promising therapeutic strategy for the treatment of OC.

Recovery sleep attenuates impairments in working memory following total sleep deprivation.

Introduction: The detrimental effects of sleep deprivation (SD) on cognitive function and quality of life are well known, and sleep disturbances are a major physical and mental health issue worldwide. Working memory plays an important role in many complex cognitive processes. Therefore, it is necessary to identify strategies that can effectively counteract the negative effects of SD on working memory. Methods: In the present study, we utilized event-related potentials (ERPs) to investigate the restorative effects of 8 h of recovery sleep (RS) on working memory impairments induced by total sleep deprivation for 36 h. We analyzed ERP data from 42 healthy male participants who were randomly assigned to two groups. The nocturnal sleep (NS) group completed a 2-back working memory task before and after normal sleep for 8 h. The sleep deprivation (SD) group completed a 2-back working memory task before and after 36 h of total sleep deprivation (TSD) and after 8 h of RS. Electroencephalographic data were recorded during each task. Results: The N2 and P3 components-which are related to working memory-exhibited low-amplitude and slow-wave characteristics after 36 h of TSD. Additionally, we observed a significant decrease in N2 latency after 8 h of RS. RS also induced significant increases in the amplitude of the P3 component and in the behavioral indicators. Discussion: Overall, 8 h of RS attenuated the decrease in working memory performance caused by 36 h of TSD. However, the effects of RS appear to be limited.

Cortical thinning in male obstructive sleep apnoea patients with excessive daytime sleepiness.

Background and purpose: Obstructive sleep apnoea is associated with excessive daytime sleepiness due to sleep fragmentation and hypoxemia, both of which can lead to abnormal brain morphology. However, the pattern of brain structural changes associated with excessive daytime sleepiness is still unclear. This study aims to investigate the effects of excessive daytime sleepiness on cortical thickness in patients with obstructive sleep apnoea. Materials and methods: 61 male patients with newly diagnosed obstructive sleep apnoea were included in the present study. Polysomnography and structural MRI were performed for each participant. Subjective daytime sleepiness was assessed using the Epworth Sleepiness Scale score. Surface-based morphometric analysis was performed using Statistical Parametric Mapping 12 and Computational Anatomy 12 toolboxes to extract cortical thickness. Results: Using the median Epworth Sleepiness Scale score, patients were divided into the non-sleepiness group and the sleepiness group. The cortical thickness was markedly thinner in the sleepiness group in the left temporal, frontal, and parietal lobe and bilateral pre- and postcentral gyri (pFWE < 0.05). There was a significant negative correlation between the cortical thickness and the Epworth Sleepiness Scale score. After adjusting for age, body mass index, and obstructive sleep apnoea severity, the Epworth Sleepiness Scale score remained an independent factor affecting the cortical thickness of the left middle temporal lobe, transverse temporal and temporal pole. Conclusion: Subjective daytime sleepiness is associated with decreased cortical thickness, and the Epworth Sleepiness Scale score may be of utility as a clinical marker of brain injury in patients with obstructive sleep apnoea.

Congenital Intestinal Malrotation in Newborns: Laparoscopic Ladd's Procedure versus Open Laparotomy.

OBJECTIVE: To assess the efficacy and safety of laparotomic or laparoscopic Ladd's procedure in newborns with congenital malrotation. STUDY DESIGN: Descriptive study. PLACE AND DURATION OF STUDY: Department of Pediatric Surgery, Ganzhou Maternal and Child Health Care Hospital, Ganzhou JiangXi province, China, from January 2015 to December 2021. METHODOLOGY: The clinical data of newborns with malcorrection were retrospectively analysed. Patients were divided into laparotomy group (64 cases) and laparoscopy group (30 cases), according to the surgery they had been subjected. The patients who had the severe malformations, underwent the laparoscopic Ladd's procedure at the first 10 cases, and had found bowel necrosis during operation were excluded. The general data such as lengths of operation, intraoperative blood loss, time-to-diet, lengths of hospital stay, and postoperative complications were compared between the two groups. RESULTS: Crude comparisons showed that the laparoscopy increased the lengths of operative time (70.0 vs. 110.0 minutes, p <0.001) but decreased the postoperative complications (25.0% vs. 6.7%, p=0.035). The intraoperative blood loss, time-to-diet, and lengths of hospital stay between the two groups were not statistically significant (p=0.109, 0.065, and 0.858 respectively). The intestinal volvulus in the two groups (43.8% vs. 80.0%, p=0.001) had statistical differences. Using modified Poisson regression analysis, adjusting for confounding differences of midgut volvulus, lengths of operation time and intraoperative blood loss, and laparoscopic Ladd's showed a significant decrease in postoperative complications (RR=0.13,95%CI 0.03-0.54, p=0.005). CONCLUSION: Laparoscopic Ladd's procedure is feasible to treat neonatal malrotation and is associated with lower postoperative complications of newborns with congenital malrotation. KEY WORDS: Newborns, Congenital malrotation, Laparoscopy, Laparotomy, Complications.

Polymeric nanoparticles-Promising carriers for cancer therapy.

Polymeric nanoparticles (NPs) play an important role in controlled cancer drug delivery. Anticancer drugs can be conjugated or encapsulated by polymeric nanocarriers, which are known as polymeric nanomedicine. Polymeric nanomedicine has shown its potential in providing sustained release of drugs with reduced cytotoxicity and modified tumor retention, but until now, few delivery systems loading drugs have been able to meet clinical demands, so more efforts are needed. This research reviews the current state of the cancer drug-loading system by exhibiting a series of published articles that highlight the novelty and functions from a variety of different architectures including micelles, liposomes, dendrimers, polymersomes, hydrogels, and metal-organic frameworks. These may contribute to the development of useful polymeric NPs to achieve different therapeutic purposes.

Effect of Propofol Intravenous Anesthesia Combined with Press-Needle Therapy on Analgesic Effect during Painless Abortion.

Objective: To discover the effect of propofol intravenous anesthesia along with press-needle therapy on analgesic effect during painless abortion. Methods: A total of 128 cases who experienced painless abortion in our hospital from January 2019 to August 2021 were recruited as the research subjects. They were categorized into control and observation groups through the haphazard number table approach, with 64 patients in each group. Propofol intravenous anesthesia was given to the control group, and the observation group was given combined anesthesia with press-needle on this basis. Ramsay score, hemodynamic indexes, operation-related indexes, and postoperative recovery were studied between the two groups before anesthesia (T0), at the time of uterine aspiration (T1), promptly following the operation (T2), and at the recovery time of directional force (T3). The stress state and the level of pain mediators in the two groups of sufferers were observed at each time period, and the visual analogue scale (VAS) was employed to assess the degree of postoperative uterine contraction pain. Results: Ramsay score at T1 and T2 time points in observation group was lesser than that in control group (P < 0.05). There existed no meaningful discrepancies in operation time and recovery time between both groups (P > 0.05). The total dosage of propofol in the observation group was lesser compared to that in the control group, and the recovery time of directional force was much shorter compared to that in the control group (P < 0.05). There existed no meaningful discrepancies in perioperative diastolic blood pressure (DBP), systolic blood pressure (SBP), and heart rate (HR) between both groups (P > 0.05). The levels of norepinephrine (NE), cortisol (Cor), glucose (GLU) and substance P (SP), prostaglandin E2 (PGE2), and 5-hydroxytryptophan (5-HT) in the observation group were lesser than those in the control group immediately after surgery and 24 hours following the operation (P < 0.05). There existed no meaningful discrepancies in vaginal bleeding time, endometrial thickness 3 weeks after operation, and time to start menstruating between both groups (P > 0.05). The score of VAS for the observation group was lesser than that of the control group at 10 min and 30 min after operation (P < 0.05). There existed no substantial discrepancy in the incidence of negative reactions between both groups (P > 0.05). Conclusion: Propofol intravenous anesthesia combined with press-needle therapy can ameliorate the analgesic impacts during painless abortion, reduce postoperative uterine contraction pain, inhibit the release of postoperative pain mediators, and improve the stress state of the body.

Cost-Effectiveness Analysis of the Application of a Porcine-Derived Fibrin Sealant for the Treatment of Cerebrospinal Fluid Leak in China.

PURPOSE: This study aimed to evaluate the cost-effectiveness of a porcine-derived fibrin sealant (PFS) for treating cerebrospinal fluid (CSF) leaks in cranial surgery compared with sutures alone from the perspective of public hospital management in China. METHODS: A decision tree model of cranial surgery patients with intraoperative CSF leak was constructed in R 3.6.3. The cost-effectiveness of using PFS with dural sutures was compared versus using sutures alone. Efficacy and safety data were obtained from a randomized controlled, single-blinded clinical trial that enrolled 200 patients (NCT03110783). Effectiveness was measured as the success rate of CSF leak treatment and the rate of postoperative complication. Hospital procurement costs were used to provide cost measurements from the hospital administrator's perspective. FINDINGS: The PFS strategy had a higher success rate of CSF leak treatment (97.81% vs 49.21%) and a lower complication rate (9.49% vs 14.29%), based on results from the clinical trial. Using PFS also resulted in cost savings amounting to $374.97 in additional intraoperative CSF leak repairs ($18.07 vs $393.04) and $66.68 in postoperative complication treatment ($131.90 vs $198.58). Both one-way sensitivity analysis and probabilistic sensitivity analysis confirmed that the model results were stable against input variations. IMPLICATIONS: The decision tree analysis revealed that using PFS in conjunction with sutures was associated with improved clinical performance and lower overall costs. PFS in combination with sutures is the dominant strategy for treating CSF leak from the perspective of hospital decision-makers.

Transcription factor McWRKY71 induced by ozone stress regulates anthocyanin and proanthocyanidin biosynthesis in Malus crabapple.

In plants, anthocyanins and proanthocyanidins (PAs) play important roles in plant resistance to abiotic stress. In this study, ozone (O3) treatments caused the up-regulation of Malus crabapple structural genes McANS, McCHI, McANR and McF3H, which promoted anthocyanin and PA accumulation. We identified the WRKY transcription factor (TF) McWRKY71 by screening differentially expressed genes (DEGs) that were highly expressed in response to O3 stress from an RNA sequencing (RNA-seq) analysis. Overexpressing McWRKY71 increased the resistance of 'Orin' apple calli to O3 stress and promoted the accumulation of anthocyanins and PAs, which facilitated reactive oxygen species scavenging to further enhance O3 tolerance. Biochemical and molecular analyses showed that McWRKY71 interacted with McMYB12 and directly bound the McANR promoter to participate in the regulation of PA biosynthesis. These findings provide new insights into the WRKY TFs mechanisms that regulate the biosynthesis of secondary metabolites, which respond to O3 stress, in Malus crabapple.

A real world cost-minimization analysis comparing the use of different endoscopic staplers in video-assisted thoracic surgery lobectomy procedures.

Aim: China's cost-containment measures increasingly focus solely on the prices of consumable medical supplies without taking a broader perspective on differences in features and overall costs. This study compared two types of endoscopic staplers in video-assisted thoracoscopic surgery (VATS) lobectomy. Materials & methods: Electronic medical records for video-assisted thoracoscopic surgery from 2016 to 2017 were collected from a hospital in Anhui province. Two cohorts were retroactively defined based on stapler type. Total costs were compared using a cost-minimization analysis model. Probabilistic sensitivity analysis was performed. Results: In the base case, the group using more expensive staplers achieved overall cost savings of about $300 per procedure. Sensitivity analysis confirmed this result in 86.5% of cases. Conclusion: A price-only supply selection strategy may have unintended cost consequences.

Economic burden of readmission due to postoperative cerebrospinal fluid leak in Chinese patients.

Aim: This real-world data study investigated the economic burden and associated factors of readmissions for cerebrospinal fluid leakage (CSFL) post-cranial, transsphenoidal, or spinal index surgeries. Methods: Costs of CSFL readmissions and index hospitalizations during 2014-2018 were collected. Readmission cost was measured as absolute cost and as percentage of index hospitalization cost. Factors associated with readmission cost were explored using generalized linear models. Results: Readmission cost averaged US$2407-6106, 35-94% of index hospitalization cost. Pharmacy costs were the leading contributor. Generalized linear models showed transsphenoidal index surgery and surgical treatment for CSFL were associated with higher readmission costs. Conclusion: CSFL readmissions are a significant economic burden in China. Factors associated with higher readmission cost should be monitored.

Determination of Physicochemical Parameters and Levels of Heavy Metals in Food Waste Water with Environmental Effects.

Bioinorganic chemistry is found as a sizzling field in today's era. It deals with chemistry amongst the heavy metals with natural resources, i.e., air, soil, water, plant byproducts (foods), and environmental essences. The aim of this research is to determine the concentration of heavy metals present in the food waste water sample and to study the environmental effects of metal ion concentration. To conduct the research work, the physicochemical parameters and levels of five heavy metals of food waste water samples were collected from five sampling points of renowned hotels, restaurants, canteens, and confectionaries of a state of India and assessed using the standard analytical procedure. Sampling was carried out from January 2017 up to December 2017. The physicochemical parameters were determined such as pH, temperature, turbidity, conductivity, total dissolved solids, total suspended solids, total alkalinity, biological oxygen demand, chemical oxygen demand, dissolved oxygen, total organic carbon, sulphate, nitrate, and phosphate. The heavy metal concentration was determined by using the UV-spectrophotometer, and the results were compared with the standards prescribed by the WHO, BIS, ICMR, and municipal authorities. The results obtained in the physicochemical analysis revealed that a few parameters were found beyond limits, and the metal ion concentration (iron and zinc) results were found above the permissible limits set by the CPCB (Central Pollution Control Board), ICMR, BIS, and World Health Organization (WHO), most especially, effluent from point P1. It was concluded that all the effluents required further treatment before releasing them into the water body or land to prevent pollution. The obtained results reveal that waste water used for irrigation and farming of nearby areas and water drained from restaurant kitchens were considerably polluted and not suitable for aquatic organisms, irrigation, and agricultural purposes.

How does Malus crabapple resist ozone? Transcriptomics and metabolomics analyses.

Ozone (O3), an oxidizing toxic air pollutant, is ubiquitous in industrialized and developing countries. To understand the effects of O3 exposure on apple (Malus) and to explore its defense mechanisms, we exposed 'Hongjiu' crabapple to O3 and monitored its responses using physiological, transcriptomics, and metabolomics analyses. Exposure to 300 nL L-1 O3 for 3 h caused obvious damage to the leaves of Malus crabapple, affected chlorophyll and anthocyanin contents, and activated antioxidant enzymes. The gene encoding phospholipase A was highly responsive to O3 in Malus crabapple. McWRKY75 is a key transcription factor in the response to O3 stress, and its transcript levels were positively correlated with those of flavonoid-related structural genes (McC4H, McDFR, and McANR). The ethylene response factors McERF019 and McERF109-like were also up-regulated by O3. Exogenous methyl jasmonate (MeJA) decreased the damaging effects of O3 on crabapple and was most effective at 200 µmol L -1. Treatments with MeJA altered the metabolic pathways of crabapple under O3 stress. In particular, MeJA activated the flavonoid metabolic pathway in Malus, which improved its resistance to O3 stress.

Classifying 2-year recurrence in patients with dlbcl using clinical variables with imbalanced data and machine learning methods.

BACKGROUND: Treatments are limited for patients with relapsed/refractory Diffuse large B-cell lymphoma (DLBCL), and their survival rate is low. Prediction of the recurrence hazard for each patient could provide a reference regarding chemotherapy regimens for clinicians to extend patients' period of long-term remission. As current strategies cannot satisfy such need, we have established predictive models to classify patients with DLBCL with complete remission who had recurrences in 2 years from ones who did not. METHODS: We assessed 518 patients with DLBCL and measured 52 variables of each patient. They were treated between January 2011 and July 2016. 17 variables were first selected by variable selection methods (including Lasso, Adaptive Lasso, and Elastic net). Then, we set classifiers and probability models for imbalanced data by combining the SMOTE sampling, cost-sensitive, and ensemble learning (consisting of AdaBoost, voting strategy, and Stacking) methods with the machine learning methods (Support Vector Machine, BackPropagation Artificial Neural Network, Random Forest), respectively. Last, assessed their performance. RESULTS: The disease stage and other 5 variables are significant indicators for recurrence. The SVM with AdaBoost ensemble learning method modeling by SMOTE data performs the best (Sensitivity=97.3%, AUC=96%, RMSE=19.6%, G-mean=96%) in all classifiers. The SVM with AdaBoost method(AUC=98.7%, RMSE=17.7%, MXE=12.7%, Cal mean=3.2%, BS0=2.5%, BS1=4%, BSALL=3.1%) and random forest (AUC=99.5%, RMSE=19.8%, MXE=16.2%, Cal mean=9.1%, BS0=4.8%, BS1=2.9%, BSALL=3.9%) both modeling by SMOTE sampling data perform well in probability models. CONCLUSIONS: This predictive model has high accuracy for almost all DLBCL patients and the six indicators can be recurrence signals.