Overexpression of CuZn superoxide dismutase improves high-density lipoprotein function in swine.

Cardiovascular disease (CVD) has been the leading cause of death worldwide. As a chronic inflammatory disease, atherosclerosis (AS) acts as the initiating factor for CVD and reactive oxygen species (ROS) play a vital role in its development. Superoxide dismutases (SOD) can alleviate the detrimental effects of ROS and serve as the first line of defense through detoxifying the products derived from oxidative stress in vivo. Considering the potential preventive effects of high-density lipoprotein (HDL) on AS and the close relationship between CuZn superoxide dismutase (CuZnSOD) and HDL, the present work investigated whether CuZnSOD overexpression in swine could improve the function of HDL. Seven CuZnSOD transgenic swine, constructed by sperm and magnetic nanoparticles, demonstrated overexpressed CuZnSOD in the liver (P < 0.01) but comparable level to control in plasma (P > 0.05). CuZnSOD overexpression significantly down-regulated the levels of triglyceride (TG), apolipoprotein A-I (apoA-I) (P < 0.05), and high-density lipoprotein cholesterol (HDL-C) (P < 0.01) in plasma. In the presence of CuZnSOD overexpression, HDL3 significantly inhibited levels of IL-6 and TNF-α induced by oxidized low-density lipoprotein (oxLDL) (P < 0.05), indicating enhanced anti-inflammatory activity of HDL. At the same time, HDL-mediated cholesterol efflux did not decrease (P > 0.05). CuZnSOD overexpression improves the anti-inflammatory function of HDL despite decreased levels of HDL-C. In Conclusion, CuZnSOD overexpression improves HDL function in swine.

Risk factors for high-stage histological chorioamnionitis among pregnancies with cervical incompetence.

AIM: The study aimed to identify predictive risk factor to identify high-stage histological chorioamnionitis (HCA) in pregnancies with cervical incompetence (CIC). METHODS: A retrospective cohort study was conducted by including 116 pregnant women with cervical incompetence that required prophylactical and therapeutical cerclage. The histopathology examination on placenta was conducted with informed patient consent. All the cases included in this study were divided based on the severity degree of HCA. The demographic characteristic and the parameters related to maternal and fetal outcome were all analyzed. Besides, perioperative parameters of cerclage, including cervical length, cervical morphology, and laboratory indexes were also compared between two groups. Univariate and multivariate logistic regression analysis were used to determine the risk factor of severe chorioamnionitis. RESULTS: Severe HCA was significantly associated with cervical morphology, cerclage indication, cerclage type, and cervical length measured via ultrasound and vaginal examination. After adjusted for confounders, V-type funneling and short cervix was indicated as independent risk factors of severe HCA by multivariate logistic regression analysis, respectively. CONCLUSIONS: V-type funneling and short cervix may indicate the elevated risk of high-stage HCA. Due to the negative outcomes related with high-stage HCA, appropriate prenatal treatment would improve the pregnancy outcomes in cerclaged population. To facilitate postpartum treatment, placental histological examination should be routinely recommended to identify the high-stage HCA, especially in high risk pregnancies.

Paired protein kinases PRKCI-RIPK2 promote pancreatic cancer growth and metastasis via enhancing NF-κB/JNK/ERK phosphorylation.

BACKGROUND: Protein kinases play a pivotal role in the malignant evolution of pancreatic cancer (PC) through mediating phosphorylation. Many kinase inhibitors have been developed and translated into clinical use, while the complex pathology of PC confounds their clinical efficacy and warrants the discovery of more effective therapeutic targets. METHODS: Here, we used the Gene Expression Omnibus (GEO) database and protein kinase datasets to map the PC-related protein kinase-encoding genes. Then, applying Gene Expression and Profiling Interactive Analysis (GEPIA), GEO and Human Protein Atlas, we evaluated gene correlation, gene expression at protein and mRNA levels, as well as survival significance. In addition, we performed protein kinase RIPK2 knockout and overexpression to observe effects of its expression on PC cell proliferation, migration and invasion in vitro, as well as cell apoptosis, reactive oxygen species (ROS) production and autophagy. We established PC subcutaneous xenograft and liver metastasis models to investigate the effects of RIPK2 knockout on PC growth and metastasis. Co-immunoprecipitation and immunofluorescence were utilized to explore the interaction between protein kinases RIPK2 and PRKCI. Polymerase chain reaction and immunoblotting were used to evaluate gene expression and protein phosphorylation level. RESULTS: We found fourteen kinases aberrantly expressed in human PC and nine kinases with prognosis significance. Among them, RIPK2 with both serine/threonine and tyrosine activities were validated to promote PC cells proliferation, migration and invasion. RIPK2 knockout could inhibit subcutaneous tumor growth and liver metastasis of PC. In addition, RIPK2 knockout suppressed autophagosome formation, increased ROS production and PC cell apoptosis. Importantly, another oncogenic kinase PRKCI could interact with RIPK2 to enhance the phosphorylation of downstream NF-κB, JNK and ERK. CONCLUSION: Paired protein kinases PRKCI-RIPK2 with multiple phosphorylation activities represent a new pathological mechanism in PC and could provide potential targets for PC therapy.

A comprehensive RNA editome reveals that edited Azin1 partners with DDX1 to enable hematopoietic stem cell differentiation.

Adenosine-to-inosine RNA editing and the catalyzing enzyme adenosine deaminase are both essential for hematopoietic development and differentiation. However, the RNA editome during hematopoiesis and the underlying mechanisms are poorly defined. Here, we sorted 12 murine adult hematopoietic cell populations at different stages and identified 30 796 editing sites through RNA sequencing. The dynamic landscape of the RNA editome comprises stage- and group-specific and stable editing patterns, but undergoes significant changes during lineage commitment. Notably, we found that antizyme inhibitor 1 (Azin1) was highly edited in hematopoietic stem and progenitor cells (HSPCs). Azin1 editing results in an amino acid change to induce Azin1 protein (AZI) translocation to the nucleus, enhanced AZI binding affinity for DEAD box polypeptide 1 to alter the chromatin distribution of the latter, and altered expression of multiple hematopoietic regulators that ultimately promote HSPC differentiation. Our findings have delineated an essential role for Azin1 RNA editing in hematopoietic cells, and our data set is a valuable resource for studying RNA editing on a more general basis.

Research on the Adsorption Law of HFAD Agents on the Surface of Porous Media during Hydraulic Fracturing-Assisted Oil Displacement in Low-Permeability Reservoirs.

Adsorption loss of surfactants in porous media is one of the key factors affecting their application in low-permeability reservoirs. The hydraulic fracturing-assisted oil displacement (HFAD) technology can effectively reduce the adsorption loss of surfactants in porous media. However, the adsorption laws of HFAD agents (surfactants) during the HFAD process are still unclear. It was studied based on physical simulation experiments in this paper. The results showed that 0.3% SY-D as the HAFD agent achieved the best effect, which could reduce the oil-water interfacial tension to 0.0239 mN/m and increase the wettability index to 0.7492. In the high-pressure injection process of HFAD technology, the injection pressure and core permeability are positively correlated with the dynamic saturation adsorption capacity of the HFAD agent on the surface of porous media and the ambient temperature is negatively correlated with it. The higher the injection pressure and the larger the core permeability, the lower the dynamic saturation adsorption capacity of the HFAD agent on the porous media surface. In addition, since adsorption is an exothermic process, increasing the temperature has an inhibitory effect on adsorption. The higher the temperature, the slower the adsorption process of the HFAD agent on porous media. Among the three influencing factors, permeability has the greatest influence on the dynamic saturation adsorption capacity of the HFAD agent on the surface of core porous media, followed by injection pressure, and temperature has the least influence on it. Therefore, when implementing HFAD technology for the reservoir with low permeability, it can be considered to increase the injection pressure of HFAD technology to reduce the dynamic saturation adsorption capacity so as to increase the effective concentration of the agent. The research results have certain guiding significance for the application of HFAD technology in the field.

Mechanism of Low Chemical Agent Adsorption by High Pressure for Hydraulic Fracturing-Assisted Oil Displacement Technology: A Study of Molecular Dynamics Combined with Laboratory Experiments.

This study investigates the influence of physical parameters such as porosity, permeability, pore-throat radius, and specific surface area/volume on the adsorption capacity of surfactants in the pore surface of reservoirs. In the meantime, the hydraulic fracturing-assisted oil displacement (HFAD) technique can effectively improve the permeability and porosity of pores in the reservoir, which may affect the adsorption capacity of surfactants in low-permeability reservoirs. This may help to reduce the adsorption loss of surfactants in low-permeability reservoirs. Based on physical simulation methods, dynamic adsorption experiments were conducted to clarify the dynamic saturation adsorption capacity effect of high-pressure and low-pressure displacement agents by the HFAD technique. In addition, the molecular dynamics simulation method was used to study the effect of high-pressure conditions of HFAD on the adsorption capacity of surfactants on weakly lipophilic silica walls. Under the condition of high injection pressure by the HFAD technique, the fluid flow velocity and the initial kinetic energy of molecules increase, while the absolute value of the electrostatic potential energy in the system decreases. In addition, the van der Waals potential energy increases. In other words, the smaller the gravitational attraction experienced by the surfactant molecules during adsorption, the greater the repulsive force. Under the dual action of electrostatic force and van der Waals forces, the absolute values of the adsorption energy and the free energy decrease. The adsorption capacity of the surfactant molecules is weakened. Moreover, the decrease in adsorption capacity has little effect on the improvement of wettability, indicating that the adsorption of the surfactant reduced by HFAD technology is mostly ineffective adsorption.

Burden of Lung Cancer in China, 1990-2019: Findings from the Global Burden of Disease Study 2019.

BACKGROUND: Lung cancer is one of the most common malignant tumors in the world. It has become an increasingly important public health problem in China. In this study, we systematically assessed the lung cancer situation in China from 1990 to 2019 and provided an epidemiological knowledge base for the revision of health policies. The relevant data were extracted from the Global Burden of Disease (GBD) database. METHODS: Based on GBD 2019 data, we evaluated the incidence, prevalence, and death rates of lung cancer in China and their change trends from 1990 to 2019, making comparisons by gender and age. RESULTS: The age-standardized incidence and death rates (ASIR and ASDR, respectively) of lung cancer in China were higher than the average levels in Asia, Africa, Europe, and Oceania and also higher than those of neighboring Asian countries. Lung cancer rose from the seventh leading cause of death in 1990 to the fourth leading one in 2019, indicating that the disease burden of lung cancer is increasing. In 2019, the incidence, prevalence, and death rates of lung cancer were all higher in men than in women across all age groups. All three indices were lower in men and women <50 years old than in men and women >50 years. From 1990 to 2019, the ASIR, age-standardized prevalence rate (ASPR), and ASDR showed trends of increase (P < .05), and the rise in the ASPR (average annual percentage change [AAPC] = 1.9) was greater than those in the ASIR (AAPC = 1) and ASDR (AAPC = .8). CONCLUSIONS: From 1990 to 2019, the incidence, prevalence, and death rates of lung cancer continued to increase in China. To reduce this burden, prevention and management of known risk factors should be promoted through national policies.

Herombopag promotes platelet engraftment and decreases platelet transfusion after allogeneic hematopoietic stem cell transplantation.

The delayed platelet engraftment associated with allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a common complication and often results in increased transplant-related complications. A single-center, prospective, investigator-initiated pilot study was conducted to explore whether herombopag, a second generation thrombopoietin-receptor agonist, would promote platelet engraftment after allo-HSCT. Between 2/2022 and 06/2022, 17 individuals (median age 39; range 15-58 years) with hematological malignancies were enrolled. Herombopag was given for a median of 22 (range 14-61) days at a dose of 7.5 mg/d. The median time to neutrophil >500/µl was 11 (range 9-19) days. The median time to platelet >20 000/µl and >50 000/µl was 13 (range 8-22), and 20 (range 14-45) days, respectively. Compared with historical controls, the cumulative incidence of platelet engraftment after HSCT was significantly higher in the herombopag group (>20 000/µl at day +21, 88% vs 65%, p = .003; >50 000/µl at day +30, 65% vs. 43%, p = .001). Herombopag also reduced the units of platelet transfusion within 30 days post-SCT (3.6 ± 2.5 vs. 5.4 ± 3.2 U, p = .01). In conclusion, it seems likely that herombopag could enhance platelet engraftment after allo-HSCT.

Age-associated augmented renal clearance and low BMI trigger suboptimal vancomycin trough concentrations in children with haematologic diseases: data of 1453 paediatric patients from 2017 to 2022.

BACKGROUND: It is usually difficult for the trough concentration of vancomycin to reach the recommended lower limit of 10 mg/L per the label dose in the paediatric population. Moreover, children with haematologic diseases who suffer from neutropenia are more likely to have lower exposure of vancomycin, and the risk factors have been poorly explored. METHOD: We reviewed and analysed the initial trough concentration of vancomycin and synchronous cytometry and biochemical parameters in the blood of 1453 paediatric patients with haematologic diseases over a 6 year period, from 2017 to 2022. RESULTS: Forty-five percent of the enrolled children had vancomycin trough concentrations below 5 mg/L after receiving a dose of 40 mg/kg/day, and the multiple regression showed that age (OR = 0.881, 95% CI 0.855 to 0.909, P < 0.001), BMI (OR = 0.941, 95% CI 0.904 to 0.980, P = 0.003) and the glomerular filtration rate (OR = 1.006, 95% CI 1.004 to 1.008, P < 0.001) were independent risk factors. A total of 79.7% of the children experienced augmented renal clearance, which was closely correlated to age-associated levels of serum creatinine. The vancomycin trough concentration was higher in children with aplastic anaemia than in those with other haematologic diseases due to a higher BMI and a lower glomerular filtration rate. CONCLUSION: Age-associated augmented renal clearance and low BMI values contributed to suboptimal trough concentrations of vancomycin in children with haematologic diseases, and the effects of long-term use of cyclosporine and glucocorticoids need to be taken into account.

LcSAO1, an Unconventional DOXB Clade 2OGD Enzyme from Ligusticum chuanxiong Catalyzes the Biosynthesis of Plant-Derived Natural Medicine Butylphthalide.

Butylphthalide, a prescription medicine recognized for its efficacy in treating ischemic strokes approved by the State Food and Drug Administration of China in 2005, is sourced from the traditional botanical remedy Ligusticum chuanxiong. While chemical synthesis offers a viable route, limitations in the production of isomeric variants with compromised bioactivity necessitate alternative strategies. Addressing this issue, biosynthesis offers a promising solution. However, the intricate in vivo pathway for butylphthalide biosynthesis remains elusive. In this study, we examined the distribution of butylphthalide across various tissues of L. chuanxiong and found a significant accumulation in the rhizome. By searching transcriptome data from different tissues of L. chuanxiong, we identified four rhizome-specific genes annotated as 2-oxoglutarate-dependent dioxygenase (2-OGDs) that emerged as promising candidates involved in butylphthalide biosynthesis. Among them, LcSAO1 demonstrates the ability to catalyze the desaturation of senkyunolide A at the C-4 and C-5 positions, yielding the production of butylphthalide. Experimental validation through transient expression assays in Nicotiana benthamiana corroborates this transformative enzymatic activity. Notably, phylogenetic analysis of LcSAO1 revealed that it belongs to the DOXB clade, which typically encompasses genes with hydroxylation activity, rather than desaturation. Further structure modelling and site-directed mutagenesis highlighted the critical roles of three amino acid residues, T98, S176, and T178, in substrate binding and enzyme activity. By unraveling the intricacies of the senkyunolide A desaturase, the penultimate step in the butylphthalide biosynthesis cascade, our findings illuminate novel avenues for advancing synthetic biology research in the realm of medicinal natural products.

Transcriptome and metabolome profiling of interspecific CSSLs reveals general and specific mechanisms of drought resistance in cotton.

In order to understand the molecular mechanism of cotton's response to drought during the flowering and boll stage, transcriptomics and metabolomics were carried out for two introgression lines (drought-tolerant line: T307; drought-sensitive line: S48) which were screened from Gossypium hirsutum cv. 'Emian22' with some gene fragments imported from Gossypium barbadense acc. 3-79, under drought stress by withdrawing water at flowering and boll stage. Results showed that the basic drought response in cotton included a series of broad-spectrum responses, such as amino acid synthesis, hormone (abscisic acid, ABA) signal transduction, and mitogen-activated protein kinases signal transduction pathway, which activated in both drought-tolerant and drought-sensitive lines. However, the difference of their imported fragments and diminished sequences triggers endoplasmic reticulum (ER) protein processing, photosynthetic-related pathways (in leaves), and membrane solute transport (in roots) in drought-tolerant line T307, while these are missed or not activated in drought-sensitive line S48, reflecting the different drought tolerance of the two genotypes. Virus-induced gene silencing assay of drought-tolerant differentially expressed heat shock protein (HSP) genes (mainly in leaf) and ATP-binding cassette (ABC) transporter genes (mainly in roots) indicated that those genes play important role in cotton drought tolerant. Combined analysis of transcriptomics and metabolomics highlighted the important roles of ER-stress-related HSP genes and root-specific ABC transporter genes in plants drought tolerance. These results provide new insights into the molecular mechanisms underlying the drought stress adaptation in cotton.

Long-term cardiovascular disease mortality among 160 834 5-year survivors of adolescent and young adult cancer: an American population-based cohort study.

AIMS: Our aim was to assess the risk of cardiovascular disease (CVD) mortality in US 5-year survivors of adolescent and young adult (AYA) cancer compared with those of the general population and contemporaneous 5-year survivors of childhood cancer. METHODS AND RESULTS: A total of 160 834 5-year AYA cancer survivors (aged 15-39 years at diagnosis) were included, representing 2 239 390 person-years of follow-up. Overall, 2910 CVD deaths occurred, which was 1.4-fold [95% confidence interval (CI) 1.3-1.4] that expected in the general population, corresponding to 3.6 (95% CI 3.2-3.9) excess CVD deaths per 10 000 person-years. The highest risk of cardiac mortality was experienced after Hodgkin's lymphoma (HL), and the highest risk of cerebrovascular mortality was observed with central nervous system (CNS) tumours. Even survivors in their 6th and 7th decades of life, the risk of CVD mortality remained markedly higher than that of the matched general population. Competing risk analysis showed that the cumulative mortality of CVD was elevated among AYA cancer survivors compared with childhood cancer survivors during the whole study period. CONCLUSION: Long-term AYA cancer survivors have a greater risk of CVD mortality than the US general population and childhood cancer survivors. Vulnerable subgroups, especially survivors of HL and CNS tumours, require continued close follow-up care for cardiovascular conditions throughout survivorship.

GmbZIP152, a Soybean bZIP Transcription Factor, Confers Multiple Biotic and Abiotic Stress Responses in Plant.

Soybean is one of the most important food crops in the world. However, with the environmental change in recent years, many environmental factors like drought, salinity, heavy metal, and disease seriously affected the growth and development of soybean, causing substantial economic losses. In this study, we screened a bZIP transcription factor gene, GmbZIP152, which is significantly induced by Sclerotinia sclerotiorum (S. sclerotiorum), phytohormones, salt-, drought-, and heavy metal stresses in soybean. We found that overexpression of GmbZIP152 in Arabidopsis (OE-GmbZIP152) enhances the resistance to S. sclerotiorum and the tolerance of salt, drought, and heavy metal stresses compared to wild-type (WT). The antioxidant enzyme related genes (including AtCAT1, AtSOD, and AtPOD1) and their enzyme activities are induced by S. sclerotiorum, salt, drought, and heavy metal stress in OE-GmbZIP152 compared to WT. Furthermore, we also found that the expression level of biotic- and abiotic-related marker genes (AtLOX6, AtACS6, AtERF1, and AtABI2, etc.) were increased in OE-GmbZIP152 compared to WT under S. sclerotiorum and abiotic stresses. Moreover, we performed a Chromatin immunoprecipitation (ChIP) assay and found that GmbZIP152 could directly bind to promoters of ABA-, JA-, ETH-, and SA-induced biotic- and abiotic-related genes in soybean. Altogether, GmbZIP152 plays an essential role in soybean response to biotic and abiotic stresses.

Antiviral Activity and Pharmacokinetics of the Hepatitis B Virus (HBV) Capsid Assembly Modulator GLS4 in Patients With Chronic HBV Infection.

BACKGROUND: GLS4 is a first-in-class hepatitis B virus (HBV) capsid assembly modulator (class I) that can inhibit HBV replication by interfering with the assembly and disassembly of HBV nucleocapsid. Here, we evaluated its antiviral activity, pharmacokinetics, and tolerability in a double-blind, randomized, parallel, entecavir-controlled study. METHODS: Twenty-four patients with chronic HBV were randomized to receive a 28-day course of GLS4 (120 or 240 mg) and ritonavir (100 mg) combination (cohorts A and B, respectively) or entecavir treatment (cohort C) at a 1:1:1 ratio. Patients were followed up for 40 days in a phase 1b study. RESULTS: The GLS4/ritonavir combination was a tolerated combination for the treatment of chronic HBV infection. A total of 2, 3, and 3 subjects presented with alanine aminotransferase flare in cohorts A, B, and C, respectively. This contributed to the withdrawal of 1, 2, and 1 patient from cohorts A, B, and C, respectively. The mean Ctrough of GLS4 was 205-218 ng/mL, which was approximately 3.7-3.9 times the 90% effective concentration (55.8 ng/mL), with a lower accumulation (accumulation rate, 1.1-2.0). In cohorts A, B, and C, the mean declines in HBV DNA after 28 days of treatment were -1.42, -2.13, and -3.5 log10 IU/mL; in hepatitis B surface antigen were -0.06, -0.14, and -0.33 log10 IU/mL; in pregenomic RNA were -0.75, -1.78, and -0.96 log10 copies/mL; and in hepatitis B core antigen were -0.23, -0.5, and -0.44 log10 U/mL, respectively. CONCLUSIONS: Treatment with 120 mg GLS4 was tolerated and had antiviral activity in patients with chronic HBV infection. CLINICAL TRIALS REGISTRATION: Chinese Clinical Trial Registry; CTR20160068. http://www.chinadrugtrials.org.cn.

Kaempferol induces ROS-dependent apoptosis in pancreatic cancer cells via TGM2-mediated Akt/mTOR signaling.

BACKGROUND: Kaempferol, a natural flavonoid, exhibits anticancer properties by scavenging reactive oxygen species (ROS). However, increasing evidence has demonstrated that, under certain conditions, kaempferol can inhibit tumor growth by upregulating ROS levels. In this study, we aimed to investigate whether kaempferol effectively suppresses pancreatic cancer through upregulation of ROS, and to explore the underlying molecular mechanism. METHODS: PANC-1 and Mia PaCa-2 cells were exposed to different concentrations of kaempferol. Cell proliferation and colony formation were evaluated by CCK-8 and colony formation assays. Flow cytometry was performed to assess the ROS levels and cell apoptosis. The mRNA sequencing and KEGG enrichment analysis were performed to identify differentially expressed genes and to reveal significantly enriched signaling pathways in response to kaempferol treatment. Based on biological analysis, we hypothesized that tissue transglutaminase (TGM2) gene was an essential target for kaempferol to induce ROS-related apoptosis in pancreatic cancer. TGM2 was overexpressed by lentivirus vector to verify the effect of TGM2 on the ROS-associated apoptotic signaling pathway. Western blot and qRT-PCR were used to determine the protein and mRNA levels, respectively. The prognostic value of TGM2 was analyzed by Gene Expression Profiling Interactive Analysis (GEPIA) tools based on public data from the TCGA database. RESULTS: Kaempferol effectively suppressed pancreatic cancer in vitro and in vivo. Kaempferol promoted apoptosis in vitro by increasing ROS generation, which was involved in Akt/mTOR signaling. TGM2 levels were significantly increased in PDAC tissues compared with normal tissues, and high TGM2 expression was positively correlated with poor prognosis in pancreatic cancer patients. Decreased TGM2 mRNA and protein levels were observed in the cells after treatment with kaempferol. Additionally, TGM2 overexpression downregulated ROS production and inhibited the abovementioned apoptotic signaling pathway. CONCLUSIONS: Kaempferol induces ROS-dependent apoptosis in pancreatic cancer cells via TGM2-mediated Akt/mTOR signaling, and TGM2 may represent a promising prognostic biomarker for pancreatic cancer.

Deep Learning-Based Congestion Detection at Urban Intersections.

In this paper, a deep learning-based traffic state discrimination method is proposed to detect traffic congestion at urban intersections. The detection algorithm includes two parts, global speed detection and a traffic state discrimination algorithm. Firstly, the region of interest (ROI) is selected as the road intersection from the input image of the You Only Look Once (YOLO) v3 object detection algorithm for vehicle target detection. The Lucas-Kanade (LK) optical flow method is employed to calculate the vehicle speed. Then, the corresponding intersection state can be obtained based on the vehicle speed and the discrimination algorithm. The detection of the vehicle takes the position information obtained by YOLOv3 as the input of the LK optical flow algorithm and forms an optical flow vector to complete the vehicle speed detection. Experimental results show that the detection algorithm can detect the vehicle speed and traffic state discrimination method can judge the traffic state accurately, which has a strong anti-interference ability and meets the practical application requirements.

Genome-wide identification of MAPK cascade genes reveals the GhMAP3K14-GhMKK11-GhMPK31 pathway is involved in the drought response in cotton.

The mitogen-activated protein kinase (MAPK) cascade pathway, which has three components, MAP3Ks, MKKs and MPKs, is involved in diverse biological processes in plants. In the current study, MAPK cascade genes were identified in three cotton species, based on gene homology with Arabidopsis. Selection pressure analysis of MAPK cascade genes revealed that purifying selection occurred among the cotton species. Expression pattern analysis showed that some MAPK cascade genes differentially expressed under abiotic stresses and phytohormones treatments, and especially under drought stress. Yeast two-hybrid (Y2H) and bimolecular fluorescence complementation (BiFC) experiments showed extensive interactions between different MAPK cascade proteins. Virus-induced gene silencing (VIGS) assays showed that some MAPK cascade modules play important roles in the drought stress response, and the GhMAP3K14-GhMKK11-GhMPK31 signal pathway was demonstrated to regulate drought stress tolerance in cotton. This study provides new information on the function of MAPK cascade genes in the drought response, and will help direct molecular breeding for improved drought stress tolerance in cotton.

The effect of body mass index and creatinine clearance on serum trough concentration of vancomycin in adult patients.

BACKGROUND: The aim of this study was to evaluate the influence of patient body mass index (BMI) and estimated creatinine clearance (CrCl) on serum vancomycin concentrations to define a possible optimal dosage regimen in overweight patients based on data obtained during therapeutic drug monitoring. METHODS: This retrospective study used data collected from January 2017 to January 2019. Adult patients (n = 204) received vancomycin treatment at a dose of 1000 mg every 12 h and underwent serum monitoring. Data collected included patient disease category, sex, age, height, weight, vancomycin concentrations, and serum creatinine. The CrCl values were estimated using the Cockcroft-Gault formula. In this study, statistical comparisons were performed on the results of patients according to serum vancomycin concentration. RESULTS: Serum vancomycin concentration was significantly related to BMI (P <  0.001) and CrCl (P <  0.05) in adult patients. Furthermore, the trough serum vancomycin concentration showed a logarithmic correlation with BMI (R = - 0.5108, 95% CI: - 0.6082 to - 0.3982, P <  0.001) and CrCl (R = - 0.5739, 95% CI: - 0.6616 to - 0.4707, P <  0.001). The multivariate analysis showed that BMI and CrCl are independent contributors to the trough vancomycin concentration. Moreover, some of the patients with higher BMI (≥ 24 kg/m2) met the goal trough concentration after an adjustment from 1000 mg every 12 h to 1000 mg every 8 h. CONCLUSIONS: Serum vancomycin concentration decreases progressively with increasing BMI and the augmentation in CrCl in adult patients. The trough concentration of vancomycin should be continuously monitored for patients with a BMI ≥ 24 kg/m2, and the dosage regimen should be adjusted to reach the target trough concentration in these patients to reduce the impact of BMI.

Musashi1 Promotes Non-Small Cell Lung Carcinoma Malignancy and Chemoresistance via Activating the Akt Signaling Pathway.

BACKGROUND/AIMS: Lung cancer is one of the leading causes for cancer mortality. The poor therapeutic outcome of non-small cell lung carcinoma (NSCLC) is mainly due to late diagnosis and chemoresistance. In this study, we investigated the role of Musashi1 (MSI1) in NSCLC malignancy and chemoresistance. METHODS: Colony formation, MTT, glucose uptake and lactate production assays were employed to study lung cancer cell malignancy and chemoresistance. RT-PCR and Western blotting were performed to detect mRNA and protein expressions of genes. We used immunohistochemistry and Pearson correlation analysis to study the relationship of gene expression. RESULTS: We demonstrated that MSI1 was able to promote the proliferation and glucose metabolism of NSCLC cells, and to mediate the sensitivity to chemotherapy drugs in NSCLC cells. Importantly, we found that MSI1 could regulate the activity of Akt signaling. The regulation of NSCLC proliferation, glucose metabolism and chemoresistance by MSI1 was dependent on the modulation of the activity of the Akt signaling pathway. We also found that MSI1 was a target of miR-181a-5p, a microRNA involved in the regulation of cancer development. The expression levels of MSI1 and miR-181a-5p were negatively correlated in NSCLC. CONCLUSION: MSI1 promotes non-small cell lung carcinoma malignancy and chemoresistance via activating the Akt signaling pathway, which provides a new strategy for the therapy of NSCLC.

Room temperature continuous wave quantum dot cascade laser emitting at 7.2 µm.

We demonstrate a quantum cascade laser with active regions consisting of InAs quantum dots deposited on GaAs buffer layers that are embedded in InGaAs wells confined by InAlAs barriers. Continuous wave room temperature lasing at the wavelength of 7.2 µm has been demonstrated with the threshold current density as low as 1.89 kA/cm2, while in pulsed operational mode lasing at temperatures as high as 110 °C had been observed. A phenomenological theory explaining the improved performance due to weak localization of states had been formulated.