[Development and in vivo biomechanics of goat mobile artificial lumbar spine complex].

OBJECTIVE: Mobile artificial lumbar complex (MALC) which suitable for reconstruction after subtotal lumbar resection in goats was developed,and to test stability of the complex and postoperative lumbar segmental motor function. METHODS: Eighteen male boer goats aged from 1 to 2 years old (weighted from 35 to 45 kg) were selected and divided into control group,fusion group and non-fusion group,with 6 goats in each group. According to preoperative CT scans and MRI examinations of lumbar,the goat MALC was designed and performed by 3D printed for non-fusion group. Operation was performed on three groups respectively,and only vertebral body and disc were exposed in control group. In fusion group,L4 part of vertebral body and the upper and lower complete disc tissues were removed,and the lumbar spine bone plate fixation was performed with titanium mesh bone grafting. In non-fusion group,vertebral body and disc were removed in the same way,and MALC was implanted. AP and lateral X-rays of lumbar vertebrae in goat were taken at 6 months after surgery,in order to understand whether the plant was dislocated,displaced and fractured. Biomechanical tests were performed on the specimens by mechanical instrument to measure range of motion (ROM) of L2,3,L3,4,L4,5 intervertebral space and the overall ROM of L2-5 lumbar vertebrae. RESULTS: MALC of lumbar vertebra was designed by 3D printing,and its component artificial vertebrae and upper and lower artificial end plates were manufactured. The semi-spherical structure was fabricated by precision lathe using high-crosslinked polyethylene material,and the prosthesis was assembled. Postoperative AP and lateral X-rays of lumbar vertebra at 6 months showed the implant position of implant and MALC were good without displacement and dislocation. In vitro biomechanical test of lumbar vertebrae specimens:(1) There were no statistical significance in ROM of lumbar intervertebral space flexion and extension,lateral flexion and rotation on L3,4 and L4,5,between non-fusion group and control group (P>0.05),while ROM of fusion group was significantly reduced compared with the other two groups (P<0.05). There were no significant difference in ROM of L2,3 intervertebral flexion and extension,lateral flexion and rotation between non-fusion group and control group (P>0.05),while fusion group was significantly increased compared with the other two groups (P<0.001). (2) There was no significant difference in overall lumbar ROM of L2-5 (P> 0.05). CONCLUSION: The individual MALC could restore intervertebral height of lumbar vertebra while maintaining the stability of lumbar vertebra and re-establishing motor function of lumbar space.

Enhanced indigenous consortia for the remediation of uranium-contaminated groundwater by bioaugmentation: Reducing and phosphate-solubilizing consortia.

To investigate the strengthening effects and mechanisms of bioaugmentation on the microbial remediation of uranium-contaminated groundwater via bioreduction coupled to biomineralization, two exogenous microbial consortia with reducing and phosphate-solubilizing functions were screened and added to uranium-contaminated groundwater as the experimental groups (group B, reducing consortium added; group C, phosphate-solubilizing consortium added). ß-glycerophosphate (GP) was selected to stimulate the microbial community as the sole electron donor and phosphorus source. The results showed that bioaugmentation accelerated the consumption of GP and the proliferation of key functional microbes in groups B and C. In group B, Dysgonomonas, Clostridium_sensu_stricto_11 and Clostridium_sensu_stricto_13 were the main reducing bacteria, and Paenibacillus was the main phosphate-solubilizing bacteria. In group C, the microorganisms that solubilized phosphate were mainly unclassified_f_Enterobacteriaceae. Additionally, bioaugmentation promoted the formation of unattached precipitates and alleviated the inhibitory effect of cell surface precipitation on microbial metabolism. As a result, the formation rate of U-phosphate precipitates and the removal rates of aqueous U(VI) in both groups B and C were elevated significantly after bioaugmentation. The U(VI) removal rate was poor in the control group (group A, with only an indigenous consortium). Propionispora, Sporomusa and Clostridium_sensu_stricto_11 may have played an important role in the removal of uranium in group A. Furthermore, the addition of a reducing consortium promoted the reduction of U(VI) to U(IV), and immobilized uranium existed in the form of U(IV)-phosphate and U(VI)-phosphate precipitates in group B. In contrast, U was present mainly as U(VI)-phosphate precipitates in groups A and C. Overall, bioaugmentation with an exogenous consortium resulted in the rapid removal of uranium from groundwater and the formation of U-phosphate minerals and served as an effective strategy for improving the treatment of uranium-contaminated groundwater in situ.

Long-term glycemic variability predicts compromised development of heart failure with improved ejection fraction: a cohort study.

Background: A substantial portion of heart failure (HF) patients adherent to guideline-directed medical therapies have experienced improved ejection fraction (EF), termed HFimpEF. Glycemic variability (GV) has emerged as a critical cardiometabolic factor. However, the relation between long-term GV and the incidence of HFimpEF is still unclear. Methods: A total of 591 hospitalized HF patients with reduced EF (HFrEF, EF≤ 40%) admitted from January 2013 to December 2020 were consecutively enrolled. Repeat echocardiograms were performed at baseline and after around 12 months. The incidence of HFimpEF, defined as (1) an absolute EF improvement ≥10% and (2) a second EF > 40% and its association with long-term fasting plasma glucose (FPG) variability were analyzed. Results: During a mean follow-up of 12.2 ± 0.6 months, 218 (42.0%) patients developed HFimpEF. Multivariate analysis showed FPG variability was independently associated with the incidence of HFimpEF after adjustment for baseline HbA1c, mean FPG during follow-up and other traditional risk factors (odds ratio [OR] for highest vs. lowest quartile of CV of FPG: 0.487 [95% CI 0.257~0.910]). Evaluation of GV by alternative measures yielded similar results. Subgroup analysis revealed that long-term GV was associated with HFimpEF irrespective of glycemic levels and diabetic conditions. Conclusions: This study reveals that greater FPG variability is associated with compromised development of HFimpEF. A more stable control of glycemic levels might provide favorable effects on myocardial functional recovery in HF patients even without diabetes.

The Effect of Hormone Types, Concentrations, and Treatment Times on the Rooting Traits of Morus 'Yueshenda 10' Softwood Cuttings.

Enhancing the capacity of fruit trees to propagate via cuttings is an important endeavor for the high-quality development of the fruit industry. Optimizing the conditions for the cutting propagation of mulberry seedlings is an important factor that influences the industrial production of this plant; however, the currently used mulberry breeding technology system is not mature. In this experiment, an orthogonal design was used to intercept semi-woody shoots of Yueshenda 10 as cuttings and set different hormone concentrations (200, 500, 800, and 1000 mg/L), different hormone types (NAA, IBA, IAA, and ABT-1), and different soaking times (10, 30, 60, and 120 min) for cuttings. The effects of the three factors on the rooting of mulberry cuttings were investigated by soaking the cuttings in clean water for 10 min as a control. The results showed that the primary and secondary order of the three factors affecting the rooting rate of cuttings was hormone concentration > hormone type > soaking time, and the concentration of exogenous hormones had a significant impact on all rooting indicators (p < 0.05). In addition, the rooting rate (66.24%), average number of roots (7.54 roots/plant), and rooting effect index (4.23) of Yueshenda 10 cuttings reached the optimal level when soaked with 800 mg/L ABT-1 for 30 min. The longest root length (10.20 cm) and average root length (4.44 cm) of cuttings achieved the best results when soaked with 800 mg/L NAA for 60 min and 500 mg/L NAA for 30 min, respectively. On balance, it is considered that the preferred solution is to soak the cuttings of Yueshenda 10 with 800 mg/L ABT1 solution for 0.5 h.

Transcriptomic Analysis of Heat Stress Response in Brassica rapa L. ssp. pekinensis with Improved Thermotolerance through Exogenous Glycine Betaine.

Chinese cabbage (Brassica rapa L. ssp. pekinensis) is sensitive to high temperature, which will cause the B. rapa to remain in a semi-dormancy state. Foliar spray of GB prior to heat stress was proven to enhance B. rapa thermotolerance. In order to understand the molecular mechanisms of GB-primed resistance or adaptation towards heat stress, we investigated the transcriptomes of GB-primed and non-primed heat-sensitive B. rapa 'Beijing No. 3' variety by RNA-Seq analysis. A total of 582 differentially expressed genes (DEGs) were identified from GB-primed plants exposed to heat stress relative to non-primed plants under heat stress and were assigned to 350 gene ontology (GO) pathways and 69 KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways. The analysis of the KEGG enrichment pathways revealed that the most abundantly up-regulated pathways were protein processing in endoplasmic reticulum (14 genes), followed by plant hormone signal transduction (12 genes), ribosome (8 genes), MAPK signaling pathway (8 genes), homologous recombination (7 genes), nucleotide excision repair metabolism (5 genes), glutathione metabolism (4 genes), and ascorbate and aldarate metabolism (4 genes). The most abundantly down-regulated pathways were plant-pathogen interaction (14 genes), followed by phenylpropanoid biosynthesis (7 genes); arginine and proline metabolism (6 genes); cutin, suberine, and wax biosynthesis (4 genes); and tryptophan metabolism (4 genes). Several calcium sensing/transducing proteins, as well as transcription factors associated with abscisic acid (ABA), salicylic acid (SA), auxin, and cytokinin hormones were either up- or down-regulated in GB-primed B. rapa plants under heat stress. In particular, expression of the genes for antioxidant defense, heat shock response, and DNA damage repair systems were highly increased by GB priming. On the other hand, many of the genes involved in the calcium sensors and cell surface receptors involved in plant innate immunity and the biosynthesis of secondary metabolites were down-regulated in the absence of pathogen elicitors in GB-primed B. rapa seedlings. Overall GB priming activated ABA and SA signaling pathways but deactivated auxin and cytokinin signaling pathways while suppressing the innate immunity in B. rapa seedlings exposed to heat stress. The present study provides a preliminary understanding of the thermotolerance mechanisms in GB-primed plants and is of great importance in developing thermotolerant B. rapa cultivars by using the identified DEGs through genetic modification.

Evaluation the role of soluble microbial products for denitrification sludge characteristic under starvation stress.

Physiological changes with the assist role of soluble microbial products (SMP) of preserved denitrifying sludge (DS) undergoing long-term stress of starvation under different storage temperature is extremely important. In this study, SMP extracted from DS were added into DS in starvation condition under room temperature (15-20 °C), 4 °C and -20 °C with three different bio-augmentation phases of 10, 15 and 30 days. Experimental results showed that added SMP in room temperature was optimal for preservation of DS under starvation stress with optimized dosage of 2.0 mL mL-1 sludge and bio-augmentation phase of 10 d. SMP was more effective in maintaining the specific denitrification activity of DS, and it was nearly boosted to 94.1 % of control one due to assist of 2 times SMP addition with 10 days interval of each. Under assist of SMP, extracellular polymeric substances (EPS) secretion was enhanced as the defense layer to withstand starvation stress, and the protein may be utilized as an alternative substrate to gain energy, accelerate electron transport and transfer during denitrification process. This investigation revealed the feasibility of SMP as an economical and robust strategy for preservation of DS.

HbA1c level is associated with the development of heart failure with recovered ejection fraction in hospitalized heart failure patients with type 2 diabetes.

BACKGROUND: Due to advances in medical treatments, a substantial proportion of heart failure (HF) patients with reduced left ventricular ejection fraction (EF, HFrEF) have experienced partial or complete recovery of EF, termed HFrecEF, and markedly improved clinical outcomes. In the present study, we sought to investigate the relationship between glycemic control and the incidence of HFrecEF in hospitalized HFrEF patients with type 2 diabetes mellitus (T2DM). METHODS: A total of 463 hospitalized T2DM patients with HFrEF were consecutively enrolled. Follow-up echocardiogram was performed after around 12 months. Patients who had an absolute EF improvement ≥10% and a second EF > 40% were classified into HFrecEF, and those who did not meet these criteria were defined as persistent HFrEF. RESULTS: During the 12-month follow-up, 44.5% of T2DM patients developed HFrecEF. Patients with HFrecEF had significantly lower HbA1c level than those with persistent HFrEF (6.5% [IQR 5.8% âˆ¼ 7.2%] vs. 6.7% [IQR 6.1% âˆ¼ 7.8%], P = 0.003), especially in HF of an ischemic etiology. HbA1c levels were inversely correlated with changes in EF during follow-up. After multivariate adjustment, every 1% increase in HbA1c conferred a 17.4% (OR: 0.826 [95% CI 0.701-0.968]) lower likelihood of HFrecEF. Compared to patients with good glycemic control (HbA1c ≤ 6.2%), those with poor glycemic control (HbA1c > 7.1%) had a 52.0% (OR: 0.480 [95% CI 0.281-0.811] decreased likelihood of HFrecEF. CONCLUSIONS: This study demonstrates that uncontrolled HbA1c level is associated with compromised development of HFrecEF in T2DM patients with HF, especially in those with an ischemic etiology.

DYRK2 downregulation in colorectal cancer leads to epithelial-mesenchymal transition induction and chemoresistance.

Colorectal cancer (CRC) is among the most prominent causes of cancer-associated mortality in the world, with chemoresistance representing one of the leading causes of treatment failure. However, the mechanisms governing such chemoresistance remain incompletely understood. In this study, the role of DYRK2 as a mediator of CRC cell drug resistance and the associated molecular mechanisms were assessed by evaluating human tumor tissue samples, CRC cell lines, and animal model systems. Initial analyses of The Cancer Genome Atlas database and clinical tissue microarrays revealed significant DYRK2 downregulation in CRC in a manner correlated with poor prognosis. We further generated LoVo CRC cells that were resistant to the chemotherapeutic drug 5-FU, and found that such chemoresistance was associated with the downregulation of DYRK2 and a more aggressive mesenchymal phenotype. When DYRK2 was overexpressed in these cells, their proliferative, migratory, and invasive activities were reduced and they were more prone to apoptotic death. DYRK2 overexpression was also associated with enhanced chemosensitivity and the inhibition of epithelial-mesenchymal transition (EMT) induction in these LoVo 5-FUR cells. Co-immunoprecipitation assays revealed that DYRK2 bound to Twist and promoted its proteasomal degradation. In vivo studies further confirmed that the overexpression of DYRK2 inhibited human CRC xenograft tumor growth with concomitant Twist downregulation. Overall, these results thus highlight DYRK2 as a promising therapeutic target in CRC worthy of further investigation.

Glutamic Acid and Poly-γ-glutamic Acid Enhanced the Heat Resistance of Chinese Cabbage (Brassica rapa L. ssp. pekinensis) by Improving Carotenoid Biosynthesis, Photosynthesis, and ROS Signaling.

Heat stress is one of the most common agrometeorological risks in crop production in the middle and lower reaches of the Yangtze River in China. This study aimed to investigate whether glutamic acid (Glu) or poly-γ-glutamic acid (γ-PGA) biostimulants can improve the thermotolerance of a cool-season Chinese cabbage (Brassica rapa L. ssp. pekinensis) crop. Priming with Glu (2.0 mM) or γ-PGA (20 mg·L-1) was conducted at the third leaf stage by applying as daily foliar sprays for 5 days before 5 days of heat stress (45 °C in 16-h light/35 °C in 8-h dark). Coupled with morpho-physiological and biochemical analyses, transcriptomes of Glu or γ-PGA-primed Chinese cabbage under heat stress were examined by RNA-seq analysis. The results showed that the thermotolerance conferred by Glu and γ-PGA priming was associated with the increased parameters of vegetative growth, gas exchange, and chlorophyll fluorescence. Compared with the control, the dry weights of plants treated with Glu and γ-PGA increased by 51.52% and 39.39%, respectively. Glu and γ-PGA application also significantly increased the contents of total chlorophyll by 42.21% and 23.12%, and carotenoid by 32.00% and 24.00%, respectively. In addition, Glu- and γ-PGA-primed plants markedly inhibited the levels of malondialdehyde, electrolyte leakage, and super-oxide anion radical, which was accompanied by enhanced activity levels of superoxide dismutase (SOD), catalase (CAT), ascorbate peroxidase (APX), and peroxidase (POD). Enrichment analysis of Kyoto Encyclopedia of Genes and Genomes (KEGG) categories within the differentially expressed genes (DEGs) functional clusters of RNA-seq data indicated that the expression levels of the genes for DNA replication, DNA repair system, linoleic acid metabolism, cysteine and methionine metabolism, glutathione metabolism, purine and pyrimidine metabolism, carotenoid biosynthesis, and plant-pathogen interaction were commonly up-regulated by both Glu and γ-PGA priming. Glu treatment enhanced the expression levels of the genes involved in aliphatic glucosinolate and 2-oxocarboxylic acid, while γ-PGA treatment activated carotenoid cleavage reaction to synthesize abscisic acid. Taken together, both Glu and γ-PGA have great potential for the preadaptation of Chinese cabbage seedlings to heat stress, with Glu being more effective than γ-PGA.

Serum Uric Acid Is Associated with the Progression of Left Ventricular Diastolic Dysfunction in Apparently Healthy Subjects.

Background: Left ventricular (LV) diastolic dysfunction (LVDD) is the defining feature of heart failure with preserved ejection fraction (HFpEF) and predicts subsequent incident heart failure (HF) and all-cause mortality. Mounting evidence reveals that cardiometabolic risk factors play critical roles in the development of LVDD. In this study, we sought to investigate the relation between serum uric acid (SUA) level and the progression of LVDD in apparently healthy patients. Methods: A total of 1082 apparently healthy subjects without diagnosed cardiovascular disease and LVDD were consecutively enrolled. SUA levels were measured, and repeat echocardiography and tissue Doppler imaging (TDI) were performed at baseline and during 1-year follow-up. Results: By dividing the study population based on quartiles of SUA, we found subjects in higher quartiles had greater increases in TDI-derived early diastolic velocity (e') and E (peak LV filling velocity)/e' ratios during 1-year follow-up. After multivariate adjustment, high SUA persisted to be an independent predictor for the subsequent worsening of LVDD (odds ratio: 1.351 [95% CI 1.125~1.625], per 100 µmol/L SUA). Subgroup analysis suggested that the association between SUA and LVDD development was more pronounced in subjects without other cardiometabolic risk factors involved. Factor analysis demonstrated that high SUA was the major cardiometabolic attribute in patients with LVDD progression. Conclusion: Our findings suggest that high SUA is an independent cardiometabolic risk factor for the progression of LVDD in apparently healthy subjects.

Endothelial microparticles: A mechanosensitive regulator of vascular homeostasis and injury under shear stress.

Hemodynamic shear stress (SS), a frictional force generated by blood flow, regulates vascular homeostasis. High and steady SS maintains physiological function of endothelial cells while low and disturbed SS promotes disturbance of vascular homeostasis and the development of atherosclerosis. Endothelial microparticle (EMP), a vesicular structure shed from endothelial cells, has emerged as a surrogate biomarker of endothelial injury and dysfunction. EMP release is triggered by disturbed SS in addition to multiple inflammatory cytokines. This review systematically summarizes the impact of SS on EMPs and the role of EMPs under SS in modulating vascular homeostasis and injury, including endothelial survival, vasodilation, inflammatory response, vascular permeability, and coagulation system.

Insulin Resistance Is Associated With Heart Failure With Recovered Ejection Fraction in Patients Without Diabetes.

Background Because of advances in medical treatments, a substantial proportion of patients with heart failure (HF) have experienced recovery of ejection fraction (EF), termed HF with recovered EF (HFrecEF). Insulin resistance (IR) is prevalent in HF and tightly related with prognosis. This study investigates the relationship between IR and the incidence of HFrecEF in patients who are nondiabetic. Methods and Results A total of 262 patients with HF with reduced EF (HFrEF) who were nondiabetic were consecutively enrolled. Patients were classified into HFrecEF (follow-up EF>40% and ≥10% absolute increase) or otherwise persistent HFrEF based on repeat echocardiograms after 12 months. IR was estimated by an updated homeostasis model assessment for IR (HOMA2-IR). The median HOMA2-IR level was 1.05 (interquartile range [IQR], 0.67-1.63) in our cohort of patients with HF who were nondiabetic. During follow-up, 121 (odds ratio [OR], 46.2% [95% CI 40.2-52.2]) patients developed HFrecEF. Compared with patients with HFrEF, patients with HFrecEF had significantly lower HOMA2-IR levels (0.92 [IQR, 0.61-1.37] versus 1.14 [IQR, 0.75-1.78], P=0.007), especially in nonischemic HF. Log2-transformed HOMA2-IR was inversely correlated to improvements in EF (Pearson's r=-0.25, P<0.001). After multivariable adjustment, a doubling of HOMA2-IR was associated with a 42.8% decreased likelihood of HFrecEF (OR, 0.572 [95% CI, 0.385-0.827]). Conclusions This study reveals that IR is independently associated with compromised development of HFrecEF in patients who are nondiabetic.

Effects of Different Growth Regulators on the Rooting of Catalpa bignonioides Softwood Cuttings.

(1) Background: To further improve the rapid reproduction and large-scale application of Catalpa bignonioides. (2) Methods: With young softwood cuttings from a 3-year-old C. bignonioides mother plant used as materials, the effects of indole-3-acetic acid(IAA), indolebutyric acid(IBA) and rhizogenic powder-1(ABT-1) growth regulators at different concentrations on cutting indexes and the dynamic changes in endogenous hormone contents during the rooting of the C. bignonioides cuttings were studied. (3) Results: The rooting of C. bignonioides cuttings could be divided into five stages. There were three types of rooting of adventitious roots. IBA treatment resulted in a high rooting rate and beneficial root morphology. The morphological indexes of the cutting roots after treatment with 1000 mg·L−1 IBA had the best overall quality, which was significantly higher than that of the roots in the control (CK) group (p < 0.05). Although the average longest root length (20.51 cm) under ABT-1 was the longest, its overall average rooting rate was slightly lower than that under IBA. The rooting effect under IAA was generally lower than that under IBA and ABT-1. The endogenous hormone content of the cuttings was found to be closely related to rooting; the IAA and zeatin nucleoside (ZR) content was high, and the ratios of IAA/ABA and IAA/ZR were high. The contents of gibberellin3 (GA3) and abscisic acid (ABA) were low, which had a promoting effect on the rooting of the cuttings. (5) Conclusions: All three kinds of auxin can promote rooting and, of the three treatment groups, the rooting effect of cuttings in the IBA treatment group was the strongest, with 1000 mg·L−1 being the optimum concentration.

Serum Lipid Profiles and All-Cause Mortality: A Retrospective Single Center Study on Chinese Inpatient Centenarians.

Objectives: To analyze the serum lipid profiles and investigate the relationship between the lipoprotein cholesterol levels and all-cause mortality in Chinese inpatient centenarians. Design: Retrospective study. Methods: Centenarians aged 100 years and older were admitted from January 2010 to January 2021 in our hospital. All centenarians completed a follow up visit till April 2021 of all-cause mortality and serum lipid profiles, including total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) levels. Cox proportional hazard models were used to assess the association between lipid profiles and all-cause mortality. Results: (1) These 121 centenarians on average were 100.85 ± 1.37 years old (100~107 years), including 114 males and 7 females. (2) The rate of treatment with lipid-lowering drugs was 69.4%, and the lipid-lowering drugs were mainly statins (63.6%). (3) The results of serum lipid profiles were as follows: TC 3.90 ± 0.69 mmol/L, TG 1.36 ± 0.55 mmol/L, HDL-C 1.14 ± 0.24 mmol/L, and LDL-C 2.05 ± 0.46 mmol/L. (4) The median follow-up time was 589 days (95% CI: 475, 703), and the all-cause mortality rate was 66.1%. (5) Multivariable analysis showed that higher TC level (HR = 1.968, 95% CI = 1.191-3.253, P = 0.008), lower LDL-C level (HR = 0.379, 95% CI = 0.212-0.677, P = 0.001) was independent factors contributed to all-cause mortality. Sensitivity analysis showed that the above results were stable. The therapy and complication morbidity did not present significant publication bias. Conclusions: The serum lipid profiles of Chinese inpatient centenarians were lower than those of the previous studies. Low LDL-C level was associated with an increased risk of all-cause mortality, which may indicate that more intensive lowering of LDL-C had a potential adverse effect on all-cause mortality for centenarians.

Glycine Betaine and ß-Aminobutyric Acid Mitigate the Detrimental Effects of Heat Stress on Chinese Cabbage (Brassica rapa L. ssp. pekinensis) Seedlings with Improved Photosynthetic Performance and Antioxidant System.

Heat stress is one of the major abiotic factors that limit the growth, development, and productivity of plants. Both glycine betaine (GB) and ß-aminobutyric acid (BABA) have received considerable attention due to their roles in stimulating tolerance to diverse abiotic stresses. In order to understand how GB and BABA biostimulants alleviate heat stress in a cool-weather Chinese cabbage (Brassica rapa L. ssp. pekinensis) plant, we investigated the GB- and BABA-primed heat-stressed plants in terms of their morpho-physiological and biochemical traits. Priming with GB (15 mM) and BABA (0.2 mM) was conducted at the third leaf stage by applying foliar sprays daily for 5 days before 5 days of heat stress (45 °C in 16 h light/35 °C in 8 h dark) on Chinese cabbage seedlings. The results indicate that GB and BABA significantly increased chlorophyll content, and the parameters of both gas exchange and chlorophyll fluorescence, of Chinese cabbage under heat stress. Compared with the unprimed heat-stressed control, the dry weights of GB- and BABA-primed plants were significantly increased by 36.36% and 45.45%, respectively. GB and BABA priming also greatly mitigated membrane damage, as indicated by the reduction in malondialdehyde (MDA) and electrolyte leakage through the elevation of proline content, and increased activity levels of superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), and ascorbate peroxidase (APX). Taken together, GB and BABA have great potential to enhance the thermotolerance of Chinese cabbage through higher photosynthesis performance, osmoprotection, and antioxidant enzyme activity.

BHLHE41 Overexpression Alleviates the Malignant Behavior of Colon Cancer Cells Induced by Hypoxia via Modulating HIF-1α/EMT Pathway.

Objective: BHLHE41 has been shown to be a marker of tumorigenesis. Colon cancer (CC) is a common malignant tumor of colonic mucosa. This study mainly explored the mechanism of BHLHE41 in alleviating malignant behavior of hypoxia-induced CC cells. Methods: The levels of BHLHE41 in CC and normal cell lines were tested by Western blot and qRT-PCR. After, CC cells were subjected to hypoxia treatment and BHLHE41 overexpression transfection, and the BHLHE41 expression, the effect of BHLHE41 on CC cell viability, apoptosis, migration, and invasion and cell cycle were tested by qRT-PCR and relevant cell functional experiments. HIF-1α and epithelial-mesenchymal transition- (EMT-) related proteins were tested by Western blot. Moreover, CC tumor-bearing model was established in nude mice, and the effect of BHLHE41 on the tumor was evaluated by measuring the tumor volume and weight. Then, the expressions of BHLHE41 and EMT-related proteins were detected by immunohistochemistry and Western blot. Results: Western blot and qRT-PCR showed that BHLHE41 was lowly expressed in CC cells. BHLHE41 overexpression could inhibit the hypoxia-induced CC cell viability, migration, and invasion, induce apoptosis, and alter cell cycle. Besides, BHLHE41 overexpression could enhance the levels of E-cadherin but reduce the levels of HIF-1α, N-cadherin, vimentin, and MMP9 in hypoxia-induced CC cells. Moreover, BHLHE41 overexpression reduced tumor volume, weight, and EMT-related proteins levels in tumor tissues. Conclusions: BHLHE41 overexpression could mitigate the malignant behavior of hypoxia-induced CC via modulating the HIF-1α/EMT pathway.

WITHDRAWN: LncRNA USP1 Knockdown Weakens the Progression of Colorectal Cancer via Modulating UBAP2L-Smad7-TGF-ß Pathway

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Proteomic Analysis of Swertiamarin-treated BV-2 Cells and Possible Implications in Neuroinflammation.

The purpose of this study was to explore the neuroprotective role of swertiamarin on neuro-inflammation, and analyzed its potential mechanism by proteomics. We used LPS to induce a inflammatory model on BV-2 cells, then 10, 25, 50 µg/mL swertiamarin was used to treat the LPS pretreated BV-2 cells. We used ELISA to detect the effect of swertiamarin on the expression of inflammation related indicators such as IL-1ß, il-6, IL-18 and TNF-α. The proteomics based on TMT-LC-MS/MS analysis was performed to explore the anti-inflammatory effects of swertiamarin by bioinformatics analysis. We found swertiamain was able to inhibit pro-inflammatory cytokines secretion in a does dependent manner, including IL-1ß, IL-6, IL-18 and TNF-α. These results were further verified by western blot. The proteomics analysis results suggested that the potential bioprocessings which regulated by swertiamarin mainly involved in cellular response to carbon monoxide, strand displacement, palmitoleoyltransferase activity, D2 dopamine receptor binding, RNA polymerase II transcription cofactor activity. The present study may provide a promising approach to treat and prevent neuro-inflammation diseases. It is preliminarily indicated that swertiamarin will play an important role in clinical anti-neuroinflammation process in the future.

Rosmarinic acid inhibits proliferation and migration, promotes apoptosis and enhances cisplatin sensitivity of melanoma cells through inhibiting ADAM17/EGFR/AKT/GSK3ß axis.

Rosmarinic acid (RA), a naturally occurring polyphenolic compound, exerts multiple biological properties including anti-cancer. The metalloprotease, a disintegrin and metalloproteinase 17 (ADAM17), can activate ligands of the epidermal growth factor receptor (EGFR) and contribute to tumor progression. We aimed to investigate whether RA could exhibit anti-cancer effects in melanoma cells through down-regulating ADAM17. The human melanoma A375 cells were exposed to RA, then cell viability, migration, invasion, apoptosis, melanin content and the expression of ADAM17/EGFR/AKT/GSK3ß were evaluated. The viability of cells exposed to RA in the presence of cisplatin (Cis) was measured by CCK-8. Cells were overexpressed with ADAM17 in the absence or presence of RA and ADAM17 inhibitor (TACE prodomain; TPD) co-treatment, then the above cellular processes were also observed. Results showed that A375 cells treated with RA showed significant lower cell viability, proliferation, migrative and invasive abilities, melanin content and expression of related proteins including MMP2 and MMP9, compared with normal cells. RA enhanced the ratio of TUINEL-positive cells, the expression of pro-apoptotic proteins, but reduced Bcl-2 expression. RA co-treatment increased the inhibitory effect of Cis on cell viability. RA inhibited the expression of ADAM17/EGFR/AKT/GSK3ß, which was further suppressed by TPD. Moreover, ADAM17 overexpression blocked all the effects of RA whereas TPD treatment generated an opposite function. In conclusion, RA exerted obvious inhibitory effect on melanoma cell proliferation, migration and invasion, but promotive effect on cells apoptosis. Addition, the showing of this characteristic of RA may rely on inhibiting the expression of ADAM17/EGFR/AKT/GSK3ß axis.

TRIM14 regulates melanoma malignancy via PTEN/PI3K/AKT and STAT3 pathways.

Melanoma is one of the most aggressive cancers with poor overall survival. To date, there are still few effective methods for the treatment of melanoma. TRIM14 was previously reported to be an important oncogene in many tumors. Nevertheless, the roles of TRIM14 in melanoma remain unknown. In this study, we found that TRIM14 was abnormally upregulated in melanoma cell lines. Knockdown of TRIM14 suppressed melanoma cell proliferation, migration, invasion, epithelial-mesenchymal transition, and melanin synthesis. Overexpression of TRIM14 had opposite effects on the cellular functions of melanoma cell lines. Further study revealed that TRIM14 knockdown increased PTEN protein levels, which in turn inactivated AKT and STAT3 pathways. Moreover, blocking AKT or STAT3 pathway with a specific inhibitor could partially reverse the promotion of melanoma malignancy mediated by TRIM14 overexpression. In addition, in vivo assay also supported the above findings. These results indicated that TRIM14 might be a promising target for melanoma treatment.