LTe2 induces cell apoptosis in multiple myeloma by suppressing AKT phosphorylation at Thr308 and Ser473.

Multiple myeloma (MM) is a highly heterogeneous hematological malignancy originating from B lymphocytes, with a high recurrence rate primarily due to drug resistance. 2-((1H-indol-3-yl)methyl)-3-((3-((1H-indol-3-yl)methyl)-1H-indol-2-yl)methyl)-1H-indole (LTe2), a tetrameric indole oligomer, possesses a wide range of anticancer activities through various mechanisms. Here, we aim to explore the anti-tumor efficiency and potential downstream targets of LTe2 in MM. Its bioactivity was assessed by employing MTT assays, flow cytometry, and the 5TMM3VT mouse model. Additionally, transcriptomic RNA-seq analysis and molecular dynamics (MD) experiments were conducted to elucidate the mechanism underlying LTe2 induced MM cell apoptosis. The results demonstrated that LTe2 significantly inhibited MM cell proliferation both in vitro and in vivo, and revealed that LTe2 exerts its effect by inhibiting the phosphorylation of AKT at the Thr308 and Ser473 sites. In summary, our findings highlight the potential of LTe2 as a novel candidate drug for MM treatment and provided a solid foundation for future clinical trials involving LTe2.

Characterization of LTr1 derived from cruciferous vegetables as a novel anti-glioma agent via inhibiting TrkA/PI3K/AKT pathway.

Malignant glioma is the most fatal, invasive brain cancer with limited treatment options. Our previous studies show that 2-(indol-3-ylmethyl)-3,3'-diindolylmethane (LTr1), a major metabolite of indole-3-carbinol (I3C) derived from cruciferous vegetables, produces anti-tumour effect against various tumour cell lines. In this study we characterized LTr1 as a novel anti-glioma agent. Based on screening 134 natural compounds and comparing the candidates' efficacy and toxicity, LTr1 was selected as the lead compound. We showed that LTr1 potently inhibited the viability of human glioma cell lines (SHG-44, U87, and U251) with IC50 values of 1.97, 1.84, and 2.03 µM, respectively. Furthermore, administration of LTr1 (100,300 mg· kg-1 ·d-1, i.g. for 18 days) dose-dependently suppressed the tumour growth in a U87 xenograft nude mouse model. We demonstrated that LTr1 directly bound with TrkA to inhibit its kinase activity and the downstream PI3K/AKT pathway thus inducing significant S-phase cell cycle arrest and apoptosis in SHG-44 and U87 cells by activating the mitochondrial pathway and inducing the production of reactive oxygen species (ROS). Importantly, LTr1 could cross the blood-brain barrier to achieve the therapeutic concentration in the brain. Taken together, LTr1 is a safe and promising therapeutic agent against glioma through inhibiting TrkA/PI3K/AKT pathway.

Spatio-Temporal Variation and Its Driving Forces of Soil Organic Carbon along an Urban-Rural Gradient: A Case Study of Beijing.

Rapid urbanization has reshaped land cover and the ecological environment, potentially improving or deteriorating soil organic carbon (SOC). However, the response of SOC to urbanization has not yet been fully exploited. Herein, by using the land-use transfer matrix, the Sen & Mann-Kendall tests, the Hurst index, and a geographical and temporal weighted regression (GTWR) model, as well as an urban-rural gradient perspective, we assessed the dynamic response of SOC to Beijing's urbanization from 2001 to2015 and identified the main drivers. The results found that SOC stock decreased by 7651.50 t C during the study period. SOC density varied significantly along an urban-rural gradient, with high value areas mainly being located in remote mountainous rural areas and low value areas mainly being located in urban areas on the plains. There was an uneven variation in SOC density across the urban-rural gradient, with suburban areas (25-40 km away from urban cores) losing the most SOC density while urban areas and rural areas remained relatively unchanged. GTWR model revealed the spatio-temporal non-flat stability of various driving forces. Precipitation, the proportion of forest, the proportion of grassland, the population, distance to the urban center, the slope, and the silt content are the main factors related to SOC stock change. As a result, we suggest policy makers reconceptualize the uneven variation in the SOC between urban and rural areas, emphasize suburban areas as a target for controlling SOC loss, and take into consideration the spatial and temporal heterogeneity of the factors influencing SOC stock when evaluating policies.

A multicenter retrospective study of transurethral prostate split for benign prostate hyperplasia.

Background: Transurethral split of the prostate (TUSP) is effective in treating benign prostatic hyperplasia (BPH). However, there is still a lack of research focusing on the optimal target population for TUSP. This study aimed to compare the efficacy of TUSP in patients with different prostate volumes or ages. Methods: The study was a multicenter retrospective study. The outcomes of TUSP in BPH patients with different prostate volumes or different ages were compared. A total of 439 patients were included in the study. Patients were divided into two groups according to prostate volume, with a cut-off value of 50 mL. Similarly, the cut-off value for the age groups was 70 years. Baseline patient characteristics and perioperative outcomes were recorded. Follow-up was performed at 1, 6, and 12 months after surgery. Results: The mean age of the patients was 73.4 years, and the mean prostate volume was 51.2 mL. At 12-month follow-up after TUSP treatment, the patients' International Prostate Symptom Scores (IPSS), quality of life (QoL) scores, and postvoid residual (PVR) volumes decreased significantly, while peak urinary flow rate (Qmax) increased significantly. Intraoperative hemoglobin (Hb) reduction was significantly lower in the small volume group than in the large volume group. The incidence of postoperative urinary urgency and transient incontinence was lower in the small volume group. IPSS score, PVR, and Qmax in the small volume group showed more remarkable changes at several time points compared to the preoperative period. Postoperative pain scores were higher in the small volume group than in the large volume group. There were no differences between the two groups in terms of long-term complications. The younger group showed greater variation in PVR and Qmax at some time points but less variation in QoL than the older group. Conclusions: TUSP is overall safe and effective in treating BPH. This study showed differences in the outcomes of TUSP in treating different prostate volumes or ages of BPH patients. The optimal surgical approach for BPH patients might be selected clinically based on a combination of prostate volume or patient age.

Efficacy and safety of mechanical thrombectomy for M2 segment of middle cerebral artery: a systematic review and meta-analysis.

BACKGROUND AND PURPOSE: The efficacy and safety of mechanical thrombectomy (MT) for M2 segment occlusion of middle cerebral artery in patients with acute ischemic stroke (AIS) was investigated. METHODS: We searched PubMed and EMBASE from inception to 16 April 2019 for relevant studies, calculated the pool relative risks (RRs) of 3-month functional independence (modified Rankin scale score 0-2), death and symptomatic intracerebral hemorrhage (sICH) in MT for M2 segment occlusion in patients with AIS versus those of M1 segment or best medical care. RESULTS: Nine studies enrolling 2152 patients compared MT for patients with AIS of M2 segment occlusion and those of M1 segment occlusion. MT for M2 occlusion had a higher rate of 3-month functional independence compared to the patients with M1 occlusion. (RR 1.27, 95% CI 1.11-1.44, P < 0.001) and decreased death (RR 0.74; 95% CI 0.58-0.96, P = 0.022) with similar risk of sICH (RR 1.11; 95% CI 0.65-1.87, P = 0.707). Four studies enrolling 1016 patients compared MT and best medical care for patients with AIS of M2 occlusion. MT for M2 occlusion benefit more than best medical care on 3-month functional independence (RR 1.43, 95% CI 1.08-1.90, P = 0.011) and death (RR 0.46; 95% CI 0.22-0.96, P = 0.022) with similar risk of sICH (RR 1.65; 95% CI 0.66-4.13; P = 0.286). CONCLUSION: MT for M2 segment benefit patients with AIS on 3-month functional independence compared with that of M1 segment or medical care, without increasing the risk of sICH.

Improving the Buffer Energy Absorption Characteristics of Movable Lander-Numerical and Experimental Studies.

To improve the soft-landing crash performance of the movable lander (ML), this study presents an investigation of a newly designed gradual energy-absorbing structure subjected to impact loads using an ML for theoretical calculation and numerical simulations. In this work, we present a novel computational approach to optimizing the energy absorption (EA) of the ML. Our framework takes as inputting the geometrical parameter (GP) as well as EA. The finite element model of the HB1, HB2, and HB3 was established and effectively verified using numerical simulation and experimental data. The relationship between the GP of the buffer material and the EA was obtained through static experiment and impact experiment, and the cushioning performance of the lander was optimized according to the ML load mass, contact speed, and EA function. According to the optimization results, we chose an outer diameter of 240 mm, an inner diameter of 50 mm, heights of HB1 = 140 mm, HB2 = 110 mm, and HB3 = 225 as the collocation, and completed the numerical simulation of three different cases. By comparing the results of theoretical calculation and numerical simulation experiments, it can be found that the overload response rates of the main body in 4 type landing, 2-2 type landing, and 1-2-1 type landing are 4.72 G, 2.61 G, and 2.33 G, respectively. It also laid the foundation for the theoretical and methodological research of the ML and manned lander in the future.

A meta-analysis of collateral status and outcomes of mechanical thrombectomy.

OBJECTIVES: To perform a systematic review and meta-analysis to investigate pretreatment collaterals and outcomes of mechanical thrombectomy in patients with acute ischemic stroke of large-vessel occlusion in anterior circulation. METHODS: We systematically searched Embase, PubMed, and the Cochrane Library from their dates of inception to March 5, 2020, and also manually searched reference lists of relevant articles. Pooled relative risk with 95% confidence interval on the association between good collaterals and functional independence (in terms of mRS 0-2), symptomatic intracranial hemorrhage, mortality, and successful reperfusion were synthesized using a random-effects model. RESULTS: Thirty-four studies enrolling 5768 patients were included in analysis. Good collaterals were significantly associated with functional independence (RR 1.93, 95%CI 1.64-2.27, P < .0001), successful reperfusion (RR 1.23, 95%CI 1.12-1.35, P < .0001), decreased rate of symptomatic intracranial hemorrhage (RR 0.68, 95%CI 0.47-0.97, P = .032), and mortality (RR 0.37, 95%CI 0.27-0.52, P < .0001). The results were consistent in sensitivity analysis. The associations between good collaterals and reperfusion remained stable after adjusting for publication bias. CONCLUSIONS: Good pretreatment collaterals were associated with functional independence, successful reperfusion, and decreased rate of sICH and mortality after receiving mechanical thrombectomy in patients with acute ischemic stroke of large-vessel occlusion.

Recycle of cotton waste by hard templating with magnesium acetate as MgO precursor.

As one of the hard-templating methods, MgO-templating was employed to recycle cotton to produce activated carbon with magnesium acetate as MgO precursor. Results showed that cotton carbonized while magnesium acetate decomposed to nanoscale MgO particles based on thermogravimetric and X-ray diffraction analysis. Carbonized residuals of cotton were able to replicate the MgO morphology thus creating pores. The size of MgO varied with impregnation ratio, treatment temperature, and time. Overall, the optimum conditions were MgO/cotton impregnation ratio 0.25, temperature 800 °C, and treatment time 60 min. Cotton-based activated carbon thus produced manifested surface area and total pore volume of 1139 m2/g and 0.85 cm3/g respectively. Both micropores and mesopores were detected based on iodine, methylene blue adsorption values, and N2 adsorption-desorption studies.

Digital gene expression profiling analysis and its application in the identification of genes associated with improved response to neoadjuvant chemotherapy in breast cancer.

BACKGROUND: This study aimed to screen sensitive biomarkers for the efficacy evaluation of neoadjuvant chemotherapy in breast cancer. METHODS: In this study, Illumina digital gene expression sequencing technology was applied and differentially expressed genes (DEGs) between patients presenting pathological complete response (pCR) and non-pathological complete response (NpCR) were identified. Further, gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were then performed. The genes in significant enriched pathways were finally quantified by quantitative real-time PCR (qRT-PCR) to confirm that they were differentially expressed. Additionally, GSE23988 from Gene Expression Omnibus database was used as the validation dataset to confirm the DEGs. RESULTS: After removing the low-quality reads, 715 DEGs were finally detected. After mapping to KEGG pathways, 10 DEGs belonging to the ubiquitin proteasome pathway (HECTD3, PSMB10, UBD, UBE2C, and UBE2S) and cytokine-cytokine receptor interactions (CCL2, CCR1, CXCL10, CXCL11, and IL2RG) were selected for further analysis. These 10 genes were finally quantified by qRT-PCR to confirm that they were differentially expressed (the log2 fold changes of selected genes were - 5.34, 7.81, 6.88, 5.74, 3.11, 19.58, 8.73, 8.88, 7.42, and 34.61 for HECTD3, PSMB10, UBD, UBE2C, UBE2S, CCL2, CCR1, CXCL10, CXCL11, and IL2RG, respectively). Moreover, 53 common genes were confirmed by the validation dataset, including downregulated UBE2C and UBE2S. CONCLUSION: Our results suggested that these 10 genes belonging to these two pathways might be useful as sensitive biomarkers for the efficacy evaluation of neoadjuvant chemotherapy in breast cancer.

Role of CA19-9 in the prognostic evaluation of SOX neoadjuvant chemotherapy for gastric cancer.

OBJECTIVE: Neoadjuvant chemotherapy refers to systemic chemotherapy applied before local surgery or radiotherapy for malignant tumors. The level of certain tumor markers is an important indicator for assessing the efficacy of neoadjuvant chemotherapy. This study aimed to investigate the effect of serum CA19-9 levels on subsequent neoadjuvant chemotherapy in the treatment of gastric adenocarcinoma. METHODS: We collected 86 advanced gastric adenocarcinoma patients from January 2016 to May 2018. Patients received at least 2 cycles neoadjuvant chemotherapy with SOX (Oxaliplatin, S-1) before surgery. Effective chemotherapy was defined as producing CR or PR andineffective was defined as SD or PD. We analyze the role of serum CA19-9 level in predicting the effectiveness of neoadjuvant chemotherapy in patients with advanced gastric cancer. RESULTS: In total 86 patients, 28 patients had abnormal and 58 patients had normal serum CA19-9 levels. The positivity rate of pretreatment serum CA19-9 was higher when PR or CR was achieved (P=0.0005***). The area under the ROC curve (AUC) for CA19-9 levels was 0.720 (95% CI 0.610-0.829) (P=0.001**). CONCLUSIONS: Measurements of CA19-9 may be helpful in monitoring the efficacy of neoadjuvant chemotherapy in the treatment of patients with advanced gastric cancer and also may be able to effectively predict this effect, thereby reducing unnecessary chemotherapy.