Data-Driven Dynamic Internal Model Control.

A data-driven dynamic internal model control (D 3 IMC) scheme is proposed for unknown nonlinear nonaffine systems bypassing modeling steps. Different from the traditional internal model constructed by either a first-principle or an identified model, a dynamic internal model (DIM) is developed in this work using I/O data where a compact form dynamic linearization approach is introduced for addressing the nonlinearity and nonaffine structure. Then, the D 3 IMC is proposed with both a nominal control algorithm and an uncertainty compensation control algorithm. The former can quickly respond to the feedback errors and the latter can compensate the model-plant mismatch and external disturbances. Meanwhile, the adaptive parameter updating law in the proposed D 3 IMC method inherits the robustness against uncertainties. A nominal D 3 IMC is also designed without including the compensator when there is no exogenous disturbance since the adaptive mechanism can handle system uncertainty. Further, the results are extended and a full-form dynamic linearization-based D 3 IMC is developed to address control of nonlinear systems with more complex dynamics. All the proposed D 3 IMC methods are data-driven without need of an explicit model, and thus they are significant extensions from the traditional model-based IMC. Simulation study verifies the results.

Data-Driven Indirect Iterative Learning Control.

In this work, a data-driven indirect iterative learning control (DD-iILC) is presented for a repetitive nonlinear system by taking a proportional-integral-derivative (PID) feedback control in the inner loop. A linear parametric iterative tuning algorithm for the set-point is developed from an ideal nonlinear learning function that exists in theory by utilizing an iterative dynamic linearization (IDL) technique. Then, an adaptive iterative updating strategy of the parameter in the linear parametric set-point iterative tuning law is presented by optimizing an objective function for the controlled system. Since the system considered is nonlinear and nonaffine with no available model information, the IDL technique is also used along with a strategy similar to the parameter adaptive iterative learning law. Finally, the entire DD-iILC scheme is completed by incorporating the local PID controller. The convergence is proved by applying contraction mapping and mathematical induction. The theoretical results are verified by simulations on a numerical example and a permanent magnet linear motor example.

Construction of a pharmaceutical care mode for cancer pain patients in primary care based on the Delphi method: an effective analysis.

Objective: Pain is one of the most common symptoms of cancer patients. Patients with advanced stages of cancer are always transferred to primary medical institutions or treated with home medication due to their specific pathophysiological characteristics. Studies have shown that continuous pharmaceutical care can improve the effectiveness and safety of drug therapy for cancer pain patients in primary care, but no relevant research has been conducted in China. Based on the Delphi method, this study aims to construct a pharmaceutical care mode for cancer pain patients and analyze its effect in drug therapy treatment in primary care in China. Methods: A pharmaceutical care mode for cancer pain patients in primary care was developed through two rounds of expert consensus. A total of 200 cancer pain patients from January 2022 to January 2023 in Nanjing Drum Tower Hospital were recruited and divided into an intervention group and control group. The self-developed pharmaceutical care mode in primary care was conducted in the intervention group, while the traditional pharmaceutical care mode was conducted in the control group. Comparisons between the groups were performed in terms of pain assessment rate, reasonable rate of pain assessment, pain score, and incidence of adverse reactions. Results: The initiative of experts in the two rounds of consultation was 100%, with an authority coefficient of 0.83. The coordination coefficient of the second round was higher than that of the first round, indicating that the consistency of expert opinions was enhanced. There were 100 cases in each group, and 12 and 8 were lost to follow-up in the intervention group and control group, respectively. Compared with the control group, the intervention group had a significantly higher pain assessment rate, a reasonable rate of pain assessment, and a significantly lower pain score and incidence of adverse reactions. Conclusion: Under the scientific and reasonable mode of pharmaceutical care for cancer pain patients at the primary level, standardized drug therapy could significantly enhance the efficacy of treatment, thereby improving the quality of life of patients.

Bispecific antibody targeting both B7-H3 and PD-L1 exhibits superior antitumor activities.

Clinical application of PD-1 and PD-L1 monoclonal antibodies (mAbs) is hindered by their relatively low response rates and the occurrence of drug resistance. Co-expression of B7-H3 with PD-L1 has been found in various solid tumors, and combination therapies that target both PD-1/PD-L1 and B7-H3 pathways may provide  additional therapeutic benefits. Up to today, however, no bispecific antibodies targeting both PD-1 and B7-H3 have reached the clinical development stage. In this study, we generated a stable B7-H3×PD-L1 bispecific antibody (BsAb) in IgG1-VHH format by coupling a humanized IgG1 mAb against PD-L1 with a humanized camelus variable domain of the heavy-chain of heavy-chain antibody (VHH) against human B7-H3. The BsAb exhibited favorable thermostability, efficient T cell activation, IFN-γ production, and antibody-dependent cell-mediated cytotoxicity (ADCC). In a PBMC humanized A375 xenogeneic tumor model, treatment with BsAb (10 mg/kg, i.p., twice a week for 6 weeks) showed enhanced antitumor activities compared to monotherapies and, to some degree, combination therapies. Our results suggest that targeting both PD-1 and B7-H3 with BsAbs increases their specificities to B7-H3 and PD-L1 double-positive tumors and induces a synergetic effect. We conclude that B7-H3×PD-L1 BsAb is favored over mAbs and possibly combination therapies in treating B7-H3 and PD-L1 double-positive tumors.

A study protocol for investigating the sonographic characteristics of neonates with critical illness: an observational cohort study.

BACKGROUND: Haemodynamic instability and hypoxaemia are common and serious threats to the survival of neonates. A growing body of literature indicates that critical care ultrasound has become the optimal evaluation tool for sick neonates. However, few studies have described sonographic characteristics of haemodynamics systematically in the neonates with critical illness. This protocol describes a prospective observational cohort study aimed at (1) characterising the sonographic characteristics of the neonates with critical diseases; and (2) assessing the mortality, significant morbidity, utility of vasoactive medications, fluid resuscitation, duration of ventilation, etc. METHODS AND ANALYSIS: This is a single-centre, prospective and observational study conducted in Chengdu Women's and Children's Central Hospital from 1 December 2022 to 31 December 2027. Neonates admitted to the neonatal intensive care unit will be recruited. After inclusion, the neonates will undergo the neonatal critical care ultrasound. The data collected via case report forms include clinical variables and sonographic measures. The primary outcome is to identify the sonographic characteristics of sick neonates with different diseases, and the secondary outcome is to describe the mortality, significant morbidity, utility of vasoactive medications, fluid resuscitation and duration of ventilation. DISCUSSION: Our study provided an organised neonatal critical care ultrasound workflow, which can be applied in practice. Accordingly, this study will first set up large data on the sonographic description of the neonates with critical illness, which can help to understand the pathophysiology of the critical illness, potentially titrating the treatment. TRIAL REGISTRATION NUMBER: Chinese Clinical Trial Registry (ChiCTR2200065581; https://www.chictr.org.cn/com/25/showproj.aspx?proj=184095).

LncRNA LINC01569 promotes M2 macrophage polarization to accelerate hypopharyngeal carcinoma progression through the miR-193a-5p/FADS1 signaling axis.

Background: Long non-coding RNA (lncRNA) LINC01569 plays an important role in regulating the tumor microenvironment (TME) and macrophage polarization. However, whether it participates in the progression of hypopharyngeal carcinoma by regulating the TME remains unclear. Methods: An online database was used to analyze clinical data. Macrophage polarization was detected using qRT-PCR and flow cytometry. In vivo experiments were performed using tumor-bearing nude mice. A co-culture system of hypopharyngeal carcinoma cells and macrophages was used to explore the interactions between the two cell types. Results: LINC01569 enhancement was observed in hypopharyngeal carcinoma tumor-associated macrophages (TAMs). In IL4-induced M2 macrophages, the expression of LINC01569 increased, while LINC01569 expression declined significantly in LPS-induced M1 macrophages. SiRNA-mediated downregulation of LINC01569 inhibits IL4-induced M2 macrophage polarization. Using online databases and a dual-luciferase reporter, miR-193a-5p was confirmed as a potential downstream sponge of LINC01569. MiR-193a-5p expression decreased in IL4-mediated M2 macrophages, which was restored by LINC01569 downregulation. Additionally, LINC01569 inhibition-mediated blocking of M2 macrophage polarization was moderately abolished by transfection with the miR-193a-5p inhibitor. Fatty acid desaturase 1 (FADS1) was verified as a downstream target of miR-193a-5p, and LINC01569 downregulation-mediated inhibition of FADS1 was blocked by miR-193a-5p mimics. Importantly, LINC01569 downregulation-mediated decline in M2 macrophage polarization was abolished by miR-193a-5p mimics, which was further reversed by FADS1 knockdown. Implantation of a mixture of FaDu cells and IL4-induced macrophages promoted tumor growth and proliferation, which were abrogated by the knockdown of LINC01569 in macrophages. Using an in co-culture system of FaDu cells and macrophages in vitro, M2 macrophage-regulated cell growth and apoptosis of FaDu cells were found to be mediated by the LINC01569/miR-193a-5p signaling axis. Conclusion: LINC01569 is highly expressed in the TAMs of hypopharyngeal carcinoma. LINC01569 downregulation restrains macrophages from polarizing toward M2 through the miR-193a-5p/FADS1 signaling axis, thereby helping tumor cells escape inherent immune surveillance and promoting the occurrence and development of hypopharyngeal carcinoma.

A narrative study of unforgettable dying stories of Chinese patients in the intensive care unit: an eight-year experience.

To describe individual perspectives and reflections on unforgettable stories about dying over an eight-year period, in a mixed surgical and general intensive care unit (ICU) in China. The study was carried out at the Second Affiliated Hospital of Soochow University. The research was based on personal experience and reflection. Narrative and experiential reflection synthesis were performed for the data analysis. This was done to understand the current situation regarding dying, then to identify and analyze, and finally to put forward some suggestions regarding the experience. The discussion and preparation for death in the ICU may still require further discussion. For a better acceptance of hospice care and high quality and dignity of death and even the donation of organs, it is important that health care providers learn to talk about death with their patients, and to encourage the patients to participate in the decision-making process.

High expression of BHLHE40 promotes immune infiltration and tumor progression in thyroid cancer.

Thyroid cancer (THCA) is a common malignancy of the endocrine system which threatens people's health and life quality. It is urgent to find the marker gene of THCA. BHLHE40 is a key gene involved in tumor malignant progression. However, the role of BHLHE40 in THCA remains unclear. In this study, 346 upregulated and 302 downregulated genes were found by analyzing the Gene Expression Omnibus database. BHLHE40 was upregulated in THCA. BHLHE40 and its related differentially expressed genes were involved in cell adhesion and differentiation in THCA. Moreover, BHLHE40 was also highly expressed in THCA cells and tissues. Downregulation of BHLHE40 inhibited cell growth and metastasis. Knockdown of BHLHE40 conditioned media retarded cell migration in M2 macrophages. In addition, knockdown of BHLHE40 inhibited CD206 and CD163 expression and decreased the secretion of interleukin-10 in M2 macrophage. Therefore, BHLHE40 has the potential to be used as a biomarker of immune infiltration and tumorigenesis in THCA.

Double Dynamic Linearization-Based Higher Order Indirect Adaptive Iterative Learning Control.

In this article, a higher order indirect adaptive iterative learning control (HO-iAILC) scheme is developed for nonlinear nonaffine systems. The inner loop adopts a P -type controller whose set-point is updated iteratively by learning from the iterations. To this end, an ideal nonlinear learning control law is designed in the outer loop. It is then transferred to a linear parametric-learning controller with a corresponding parameter estimation law by introducing an iterative dynamic linearization (IDL) method. This IDL method is also used to gain an iterative linear data model of the nonlinear system. A parameter iterative updating algorithm is utilized for estimating the unknown parameters of the obtained linear data model. Finally, the HO-iAILC is presented that utilizes additional error information to improve the control performance and employs two iterative adaptive mechanisms to deal with uncertainties. The convergence of the proposed HO-iAILC scheme is proved by using two basic mathematical tools, namely: 1) contraction mapping and 2) mathematical induction. Simulation studies are conducted for the verification of the theoretical results.

Inflammatory factor tumor necrosis factor-α (TNF-α) activates P-glycoprotein (P-gp) by phosphorylating c-Jun and thus promotes transportation in placental cells.

Background: P-glycoprotein (P-gp), encoded by the ABCB1 gene, actively pumps drugs and other xenobiotics from trophoblast cells back into the maternal circulation and thus acts as one of the most critical protectors of the fetus. The effect of tumor necrosis factor-α (TNF-α) on P-gp and molecule-transporting activity remains unknown. The goal of this study was to investigate the role of TNF-α in placental molecule-transporting activity and the underlies mechanisms. Methods: Cultured human placental choriocarcinoma cell lines, Bewo, JEG-3 and JAR, were used in this study. Cultured cells were incubated with 5, 10 and 20 ng/mL of recombinant TNF-α (rTNF-α) for 24 h, respectively, for follow-up experiments. The dimer form and expression of activator protein-1 (AP-1) family members were detected using Western blot (WB) and chromatin immunoprecipitation (ChIP). mRNA and protein expression of ABCB1 were detected using reverse transcriptional quantitative polymerase chain reaction (RT-qPCR) and WB, respectively. Double luciferase labeling was used to verify the concentration of digoxin. Electromobility shift assay (EMSA) and ChIP were used to identify the binding ability of c-Jun to ABCB1 gene promoter. Proliferation and apoptosis of Bewo cells were determined using flow cytometry. Digoxin concentration were determined using dual luciferase labeling method. Results: Administration of rTNF-α upregulated the expression of c-Jun but not JunB or JunD in a dose-dependent manner and promoted the binding of c-Jun to the ABCB1 promoter region in Bewo cells. rTNF-α also increased the uptake of two P-gp-specific substrates, Rh123 and DiOC2(3), a function reversed by the addition of SP600125 and SR11302. We also found that rTNF-α increased the efflux ratio of digoxin, an outcome that was reversed, as expected, by inhibiting c-Jun and P-gp binding activities. Furthermore, we identified that rTNF-α tightly regulates the molecule-transporting activity of P-gp by promoting the phosphorylation of c-Jun. Conclusions: TNF-α activates P-gp to promote placental molecule-transporting activity by directly upregulating c-Jun expression and phosphorylation. These findings demonstrate the clinical significance of TNF-α in modulating the placental barrier, which plays an important role in protecting fetus against harmful drugs.

Development of a variant of dinutuximab with enhanced antitumor efficacy and reduced induction of neuropathic pain.

Dinutuximab (ch14.18) was the first approved monoclonal antibody against the tumor-associated antigen disialoganglioside GD2. Despite its success in treating neuroblastoma (NB), it triggers a significant amount of neuropathic pain in patients, possibly through complement-dependent cytotoxicity (CDC). We hypothesized that modifying ch14.18 using antibody engineering techniques, such as humanization, affinity maturation, and Fc engineering, may enable the development of next-generation GD2-specific antibodies with reduced neuropathic pain and enhanced antitumor activity. In this study we developed the H3-16 IgG1m4 antibody from ch14.18 IgG1. H3-16 IgG1m4 exhibited enhanced binding activity to GD2 molecules and GD2-positive cell lines as revealed by ELISA, and its cross-binding activity to other gangliosides was not altered. The CDC activity of H3-16 IgG1m4 was decreased, and the antibody-dependent cellular cytotoxicity (ADCC) activity was enhanced. The pain response after H3-16 IgG1m4 antibody administration was also reduced, as demonstrated using the von Frey test in Sprague-Dawley (SD) rats. In summary, H3-16 IgG1m4 may have potential as a monoclonal antibody with reduced side effects.

C1R, CCL2, and TNFRSF1A Genes in Coronavirus Disease-COVID-19 Pathway Serve as Novel Molecular Biomarkers of GBM Prognosis and Immune Infiltration.

Glioblastoma multiforme (GBM) is a prevalent intracranial brain tumor associated with a high rate of recurrence and treatment difficulty. The prediction of novel molecular biomarkers through bioinformatics analysis may provide new clues into early detection and eventual treatment of GBM. Here, we used data from the GTEx and TCGA databases to identify 1923 differentially expressed genes (DEGs). GO and KEGG analyses indicated that DEGs were significantly enriched in immune response and coronavirus disease-COVID-19 pathways. Survival analyses revealed a significant correlation between high expression of C1R, CCL2, and TNFRSF1A in the coronavirus disease-COVID-19 pathway and the poor survival in GBM patients. Cell experiments indicated that the mRNA expression levels of C1R, CCL2, and TNFRSF1A in GBM cells were very high. Immune infiltration analysis revealed a significant difference in the proportion of immune cells in tumor and normal tissue, and the expression levels of C1R, CCL2, and TNFRSF1A were associated with immune cell infiltration of GBM. Additionally, the protein-protein interaction networks of C1R, CCL2, and TNFRSF1A involved a total of 65 nodes and 615 edges. These results suggest that C1R, CCL2, and TNFRSF1A may be used as molecular biomarkers of prognosis and immune infiltration in GBM patients in the future.

Detection of H-type bronchoesophageal fistula in a newborn: A case report and literature review.

RATIONALE: Congenital tracheoesophageal fistula (TEF) is a rare developmental malformation. The H subtype accounts for approximately 4% of TEFs. Unlike other TEFs, the H-type is not accompanied by esophageal atresia and has nonspecific clinical symptoms, and its specific anatomical abnormalities are not always readily apparent. Furthermore, none of the currently available diagnostic methods for H-type TEF have absolute sensitivity, resulting in misdiagnoses, and accurate diagnoses are often delayed even until adulthood; in our case, we detected a congenital bronchoesophageal fistula, which is even more rare than regular H-type TEF, through a technique that was not previously reported for newborns, involving bronchoscopy, with methylene blue injected through an esophagoscope. We believe that we have provided this kind of case first in newborns.Furthermore, because there is not one literature summarizing the clinical symptoms and the effective methods up to now, we still are not clear which detective method is more efficient or accurate, especially in newborns, so it is very necessary to summarize and compare for improving the early diagnosis of TEFs; our study makes a significant contribution to the literature because we collated previously reported cases, including the clinical features and the usefulness and success rates of major tests, which will be very helpful for the early diagnosis of TEFs. PATIENT CONCERNS: A newborn male presented with an array of nonspecific clinical symptoms from birth, leading to pneumonia and mechanical ventilation. Oral feeding led to an improvement in most but not all symptoms, which returned when oral feeding was resumed. A second round of confirmatory tests was still unable to detect the cause. DIAGNOSIS: The diagnosis of H-type bronchoesophageal fistula was established through a technique that was not previously reported for newborns, involving bronchoscopy, with methylene blue injected through an esophagoscope. INTERVENTIONS: The surgery was performed after diagnosis, and the bronchoesophageal fistula was successfully repaired. OUTCOMES: The patient was discharged on postoperative day 7, and his status was reported to be normal at a follow-up visit 8 months after surgery. LESSONS: H-type TEF is a rare congenital abnormality, and its early diagnosis is highly difficult, especially bronchoesophageal fistula. Increased oral saliva and air-filled stomachs are characteristic manifestations. Bronchoscopy combined with esophagoscopy can improve the rate of early diagnosis. A combination of tests can improve the detection rate.

Risk Factors of Mechanical Ventilation in Premature Infants During Hospitalization.

BACKGROUND: The purpose of this study was to identify the risk factors for premature neonates requiring mechanical ventilation. METHODS: Premature neonates admitted to Chengdu Women's and Children's Central Hospital between July 2014 and December 2020 were retrospectively included in this study. Clinical and demographic factors were collated. Univariate and multivariate logistic regression analyses were conducted to identify the risk factors for premature infants requiring mechanical ventilation. RESULTS: A total of 1262 premature neonates participated in the study. Among them, 423 (33.53%) neonates required mechanical ventilation, whereas 839 (66.48%) neonates did not require mechanical ventilation. Multivariate logistic regression analysis determined that a lower Apgar score at 5 min (OR = 0.595, 95% CI: 0.472-0.74; P < 0.001), lower gestational age (very preterm) (OR = 11.745, 95% CI: 4.362, 31.619, P < 0.001), lower systolic blood pressure (OR = 0.864, 95% CI: 0.812-0.917, P = 0.001), lower diastolic blood pressure (OR = 0.894, 95% CI: 0.831-0.96, P = 0.002), higher respiratory rate (OR = 1.292, 95% CI: 1.238-1.355, P < 0.001), increased C-reactive protein levels (OR=1.044, 95% CI: 1.003-1.086, P = 0.036), and presence of patent ductus arteriosus (OR = 2.174, 95% CI: 1.185-3.972, P = 0.012) were independently associated with an increased possibility of adopting mechanical ventilation in premature infants. ROC analysis demonstrated that the predicted power for premature neonates requiring mechanical ventilation was 0.855 (95% CI: 0.808-0.902, P < 0.001). CONCLUSION: In conclusion, we determined that a lower Apgar score at 5 min, lower gestational age, lower systolic blood pressure, lower diastolic blood pressure, higher respiratory rate, increased C-reactive protein levels and presence of patent ductus arteriosus were independently associated with an increased possibility of adopting mechanical ventilation in premature infants.

Hot Deformation Behavior and Microstructure Evolution of Fe-5Mn-3Al-0.1C High-Strength Lightweight Steel for Automobiles.

The hot deformation behavior of a newly designed Fe-5Mn-3Al-0.1C (wt.%) medium manganese steel was investigated using hot compression tests in the temperature range of 900 to 1150 °C, at constant strain rates of 0.1, 1, 2.5, 5, 10, and 20 s-1. A detailed analysis of the hot deformation parameters, focusing on the flow behavior, hot processing map, dynamic recrystallization (DRX) critical stress, and nucleation mechanism, was undertaken to understand the hot rolling process of the newly designed steel. The flow behavior is sensitive to deformation parameters, and the Zener-Hollomon parameter was coupled with the temperature and strain rate. Three-dimensional processing maps were developed considering the effect of strain and were used to determine safe and unsafe deformation conditions in association with the microstructural evolution. In the deformation condition, the microstructure of the steel consisted of δ-ferrite and austenite; in addition, there was a formation of DRX grains within the δ-ferrite grains and austenite grains during the hot compression test. The microstructure evolution and two types of DRX nucleation mechanisms were identified; it was observed that discontinuous dynamic recrystallization (DDRX) is the primary nucleation mechanism of austenite, while continuous dynamic recrystallization (CDRX) is the primary nucleation mechanism of δ-ferrite. The steel possesses unfavorable toughness at the deformation temperature of 900 °C, which is mainly due to the presence of coarse κ-carbides along grain boundaries, as well as the lower strengthening effect of grain boundaries. This study identified a relatively ideal hot processing region for the steel. Further exploration of hot roll tests will follow in the future.

Structure optimization of gasket based on orthogonal experiment and NSGA-II.

With the aim of enhancing both reliability and fatigue life of gasket, this study combines finite element analysis, orthogonal experimental design, dynamically-guided multi-objective optimization, and the non-dominated sorting genetic algorithm with elitist strategy to optimize the geometric parameters of the cylinder gasket. The finite element method was used to analyze the temperature field, thermal-mechanical coupling stress field, and deformation of cylinder gasket. The calculation results were experimentally validated by measured temperature data, and comparison results show that the maximum error between calculated value and experiment value is 7.1%, which is acceptable in engineering problems. Based on above results and orthogonal experiment design method, the effects of five factors, including diameter of combustion chamber circle, diameter of coolant flow hole, length of the insulation zone between third and fourth cylinders, thickness of gasket, and bolt preload, on three indexes: temperature, stress, and deformation of gasket, were examined in depth. Through the variance analysis of the results, three important factors were identified to proceed later calculation. The dynamically guided multi-objective optimization strategy and the non-dominated sorting genetic algorithm were effectively used and combined to determine the optimal geometric parameters of cylinder gasket. Furthermore, calculation results suggest that temperature, stress, and deformation of the optimized cylinder gasket have been improved by 27.88 K, 16.84 MPa, and 0.0542 mm, respectively when compared with the origin object, which shows the excellent performance of gasket optimization and effectiveness of the proposed optimization strategy.

Creep-Fatigue Experiment and Life Prediction Study of Piston 2A80 Aluminum Alloy.

In order to improve the reliability and service life of vehicle and diesel engine, the fatigue life prediction of the piston in a heavy diesel engine was studied by finite element analysis of piston, experiment data of aluminum alloy, fatigue life model based on energy dissipation criteria, and machine learning algorithm. First, the finite element method was used to calculate and analyze the temperature field, thermal stress field, and thermal-mechanical coupling stress field of the piston, and determine the area of heavy thermal and mechanical load that will affect the fatigue life of the piston. Second, based on the results of finite element calculation, the creep-fatigue experiment of 2A80 aluminum alloy was carried out, and the cyclic response characteristics of the material under different loading conditions were obtained. Third, the fatigue life prediction models based on energy dissipation criterion and twin support vector regression are proposed. Then, the accuracy of the two models was verified using experiment data. The results show that the model based on the twin support vector regression is more accurate for predicting the material properties of aluminum alloy. Based on the established life prediction model, the fatigue life of pistons under actual service conditions is predicted. The calculation results show that the minimum fatigue life of the piston under plain condition is 2113.60 h, and the fatigue life under 5000 m altitude condition is 1425.70 h.

Co-production of acetoin and succinic acid by metabolically engineered Enterobacter cloacae.

BACKGROUND: Renewable chemicals have attracted attention due to increasing interest in environmental concerns and resource utilization. Biobased production of industrial compounds from nonfood biomass has become increasingly important as a sustainable replacement for traditional petroleum-based production processes depending on fossil resources. Therefore, we engineered an Enterobacter cloacae budC and ldhA double-deletion strain (namely, EC∆budC∆ldhA) to redirect carbon fluxes and optimized the culture conditions to co-produce succinic acid and acetoin. RESULTS: In this work, E. cloacae was metabolically engineered to enhance its combined succinic acid and acetoin production during fermentation. Strain EC∆budC∆ldhA was constructed by deleting 2,3-butanediol dehydrogenase (budC), which is involved in 2,3-butanediol production, and lactate dehydrogenase (ldhA), which is involved in lactic acid production, from the E. cloacae genome. After redirecting and fine-tuning the E. cloacae metabolic flux, succinic acid and acetoin production was enhanced, and the combined production titers of acetoin and succinic acid from glucose were 17.75 and 2.75 g L-1, respectively. Moreover, to further improve acetoin and succinic acid production, glucose and NaHCO3 modes and times of feeding were optimized during fermentation of the EC∆budC∆ldhA strain. The maximum titers of acetoin and succinic acid were 39.5 and 20.3 g L-1 at 72 h, respectively. CONCLUSIONS: The engineered strain EC∆budC∆ldhA is useful for the co-production of acetoin and succinic acid and for reducing microbial fermentation costs by combining processes into a single step.

Bioinformatics analysis shows that TOP2A functions as a key candidate gene in the progression of cervical cancer.

Cervical cancer (CC) is one of the most prevalent types of cancer affecting females worldwide. However, the molecular mechanisms underlying the development and progression of CC remains to be elucidated. Taking the high incidence and mortality rates amongst women into consideration, the identification of novel biomarkers to prevent CC is of great significance and required to improve diagnosis. Using three raw microarray datasets from the Gene Expression Omnibus database, 188 differentially expressed genes (DEGs) were identified. Gene Ontology and pathway analyses were performed on the DEGs. Through protein-protein interaction network construction and module analysis, eight hub genes [cell division cycle 6, cyclin-dependent kinase 1 (CDK1), cell division control protein 45, budding uninhibited by benzimidazoles 1 (BUB1), DNA topoisomerase II α (TOP2A) and minichromosome maintenance complex component 4, CCNB2 and CCNB1] were identified, but only TOP2A was considered a prognostic factor in survival analysis. There were strong positive correlations between TOP2A and BUB1 (P<0.0001, rs=0.635), CDK1 (P<0.0001, rs=0.511), centromere protein F (CENPF) (P<0.0001, rs=0.677), Rac GTPase activating protein 1 (RACGAP1) (P<0.0001, rs=0.612), F-box protein 5 (FBXO5) (P<0.0001, rs=0.585) and BUB1 mitotic checkpoint serine/threonine kinase B (BUB1B) (P<0.0001, rs=0.584). Additionally, BUB1, CDK1, CENPF, RACGAP1, FBXO5 and BUB1B are all potentially suitable candidate targets for the diagnosis and treatment of CC. In conclusion, the present study identified TOP2A as a potential tumor oncogene and a biomarker for the prognosis of CC.

Insights into the Evolution of Neoteny from the Genome of the Asian Icefish Protosalanx chinensis.

Salangids, known as Asian icefishes, represent a peculiar radiation within the bony fish order Protacanthopterygii where adult fish retain larval characteristics such as transparent and miniaturized bodies and a cartilaginous endoskeleton into adulthood. Here, we report a de novo genome of Protosalanx chinensis, the most widely distributed salangid lineage. The P. chinensis genome assembly is more contiguous and complete than a previous assembly. We estimate that P. chinensis, salmons, trouts, and pikes diverged from a common ancestor 185 million years ago. A juxtaposition with other fish genomes revealed loss of the genes encoding ectodysplasin-A receptor (EDAR), SCPP1, and four Hox proteins and likely lack of canonical fibroblast growth factor 5 (FGF5) function. We also report genomic variations of P. chinensis possibly reflecting the immune system repertoire of a species with a larval phenotype in sexually mature individuals. The new Asian icefish reference genome provides a solid foundation for future studies.