Perturbation of METTL1-mediated tRNA N7- methylguanosine modification induces senescence and aging.

Cellular senescence is characterized by a decrease in protein synthesis, although the underlying processes are mostly unclear. Chemical modifications to transfer RNAs (tRNAs) frequently influence tRNA activity, which is crucial for translation. We describe how tRNA N7-methylguanosine (m7G46) methylation, catalyzed by METTL1-WDR4, regulates translation and influences senescence phenotypes. Mettl1/Wdr4 and m7G gradually diminish with senescence and aging. A decrease in METTL1 causes a reduction in tRNAs, especially those with the m7G modification, via the rapid tRNA degradation (RTD) pathway. The decreases cause ribosomes to stall at certain codons, impeding the translation of mRNA that is essential in pathways such as Wnt signaling and ribosome biogenesis. Furthermore, chronic ribosome stalling stimulates the ribotoxic and integrative stress responses, which induce senescence-associated secretory phenotype. Moreover, restoring eEF1A protein mitigates senescence phenotypes caused by METTL1 deficiency by reducing RTD. Our findings demonstrate that tRNA m7G modification is essential for preventing premature senescence and aging by enabling efficient mRNA translation.

The Impacts of Planting Patterns Combined with Irrigation Management Practices on Watermelon Growth, Photosynthesis, and Yield.

(1) Background: Crop yields in China's arid and semi-arid regions are limited by water shortages. Exploring the interactions and resource utilization among agroforestry species is key to maintaining diversified agricultural production. (2) Objective: An apple-watermelon agroforestry system and watermelon sole-cropping system were compared to quantify how resource availability (light, water) and watermelon performance (leaf photosynthetic rate, growth, and yield) change with irrigation strategies. (3) Methods: A three-year apple and watermelon field experiment was conducted in a young apple orchard in the arid area of central Ningxia to test the effect of light competition and irrigation systems on light environment, leaf photosynthetic rate, plant growth, and yield in watermelon. The experiment encompassed two planting patterns: (i) apple-watermelon agroforestry (AF) and watermelon sole-cropping (SC) and (ii) three irrigation quotas (W1: 105 mm, W2: 210 mm, and W3: 315 mm). (4) Results: The results show that the agroforestry planting pattern extended the growth period of watermelon and increased the leaf area index. Mean daily shade intensity increased by 16.02% from 2020 to 2022. The land equivalent ratio (LER) was >1 in 2021 and 2022. The SWC, leaf photosynthetic rate, LAI, and yield of watermelon in an agroforestry planting pattern were lower than when in a sole-cropping planting pattern. However, under the W1 irrigation strategy, the total soluble solids of the agroforestry planting pattern were 2.27% higher than those of the sole-cropping pattern, and the yield of the agroforestry planting pattern was 2.59% higher than that of the sole-cropping pattern. Under the W3 irrigation strategy, the average watermelon weight in the agroforestry planting pattern was 2.85% higher than that of the sole-cropping pattern. A path analysis showed that the agroforestry planting pattern can increase the yield by increasing soil water content, which is different from the sole-cropping pattern. (5) Conclusions: The results confirm that the apple-watermelon agroforestry planting pattern reduced watermelon yields. However, the LER of the agroforestry system was greater than 1.0. It is reasonable to plant watermelons in young apple forests.

Overexpression of Mena is associated with tumor progression and poor prognosis in oral squamous cell carcinoma via EMT.

Background: Mena, a cytoskeletal regulatory protein, is involved in actin-based regulation of cell motility and adhesion, and contributes to tumor invasion and metastasis. However, the role of Mena in oral squamous cell carcinoma remains unclear. This is the first research focusing on the prognostic value of Mena in OSCC. In this study, we aimed to investigate the correlation between Mena expression and clinicopathological significance, as well as prognostic value in OSCC. Methods: Mena gene expression profiles of OSCC and normal tissues were collected from Oncomine, TCGA, and GEO databases. Biological function was analyzed through GO, KEGG and GSEA enrichment. Further, the expression level of Mena and tumor-related markers in 151 OSCC specimens was examined by IHC staining based on tissue microarray. Kaplan-Meier analysis was used to assess the prognostic performance of Mena in OSCC. Result: Mena was generally upregulation in various malignancies, especially OSCC. The functional analyses indicated that Mena was involved in the assembly and regulation of actin, cell movement, and EMT. IHC staining revealed that high expression of Mena in OSCC was correlated with Lymphatic metastasis, TNM stage, E-cadherin, Vimentin, and MMP-2, but insignificantly Ki67. Kaplan-Meier analysis demonstrated that elevated expression of Mena was significantly associated with poor overall survival and disease-free survival of OSCC patients. Conclusion: Mena could be a novel biomarker for predicting the prognosis of OSCC patients, which supports a theoretical basis for developing molecular target therapy.

New 2-aryl-6-methyl-3,4-dihydro-ß-carbolin-2-iums as potential antifungal agents: Synthesis, bioactivity and structure-activity relationship.

Thirty new title compounds along with five known analogues were prepared from commercially available 2-arylhydrazin-1-ium chlorides and α-ketoglutaric acid. The mycelium growth rate method was used to evaluate inhibition activity against six strains of plant pathogenic fungi. Most of the compounds displayed the activity for each the fungi at 150 µΜ, higher than azoxystrobin, a positive drug. Compound 6-2 showed the lowest average IC50 value of 4.58 µg/mL for all the fungi where F. solani exhibited the highest susceptibility to most of the compounds. For F. solani, some compounds were more active with IC50 values of 2.67-8.48 µM than thiabendazole (IC50 = 9.30 µM) and/or carbendazim (IC50 = 3.36 µM). The SAR showed that the activity is significantly affected by substituents on the A-ring and/or D-ring along with the degree of unsaturation of the C-ring. Thus, a series of new ß-carboline compounds with potent antifungal potential were found.

Bioactivity and structure-activity relationship of cinnamic acid derivatives and its heteroaromatic ring analogues as potential high-efficient acaricides against Psoroptes cuniculi.

A series of cinnamic acid derivatives and its heteroaromatic ring analogues were synthesized and evaluated for acaricidal activity in vitro against Psoroptes cuniculi, a mange mite. Among them, eight compounds showed the higher activity with median lethal concentrations (LC50) of 0.36-1.07mM (60.4-192.1µg/mL) and great potential for the development of novel acaricidal agent. Compound 40 showed both the lowest LC50 value of 0.36mM (60.4µg/mL) and the smallest median lethal time (LT50) of 2.6h at 4.5mM, comparable with ivermectin [LC50=0.28mM (247.4µg/mL), LT50=8.9h], an acaricidal drug standard. SAR analysis showed that the carbonyl group is crucial for the activity. The type and chain length of the alkoxy in the ester moiety and the steric hindrance near the ester group significantly influence the activity. The esters were more active than the corresponding thiol esters, amides, ketones or acids. Replacement of the phenyl group of cinnamic esters with α-pyridyl or α-furanyl significantly increase the activity. Thus, a series of cinnamic esters and its heteroaromatic ring analogues with excellent acaricidal activity emerged.

New 2-Aryl-9-methyl-ß-carbolinium salts as Potential Acetylcholinesterase Inhibitor agents: Synthesis, Bioactivity and Structure-Activity Relationship.

A series of 2-aryl-9-methyl-ß-carbolinium bromides (B) were synthesized and explored for anti-acetylcholinesterase (AChE) activities in vitro, action mechanism and structure-activity relationship. All the compounds B along with their respective 3,4-dihydro intermediates (A) presented anti-AChE activity at 10 µM. Thirteen compounds B showed the excellent activity with IC50 values of 0.11-0.76 µM and high selectivity toward AChE relative to butyrylcholinesterase (BChE), superior to galantamine (IC50 = 0.79 µM), a selective AChE inhibitor drug. Kinetic analysis showed that the action mechanisms of both compounds B and A are a competitive inhibition model. Structure-activity relationship analyses showed that the C = N+ moiety is a determinant for the activity. Substituents at 6, 7 or 4' site, the indole-N-alkyl and the aromatization of the C-ring can significantly improve the activity. Molecular docking studies showed that the compounds could combine with the active site of AChE by the π-π or cation-π action between the carboline ring and the phenyl rings of the residues, and the ß-carboline moiety is embedded in a cavity surrounded by four aromatic residues of Trp86, Tyr337, Trp439 and Tyr449. The present results strongly suggest that the para-position of the D-ring should be a preferred modification site for further structural optimization design. Thus, 2-aryl-9-methyl-ß-carboliniums emerged as novel and promising tool compounds for the development of new AChE inhibitor agents.

Evaluation of the implementation of a 24-hr stroke thrombolysis emergency treatment for patients with acute ischaemic stroke.

AIMS AND OBJECTIVES: To assess the trends of intravenous (IV) thrombolysis with recombinant tissue plasminogen activator (rt-PA) among patients with acute ischaemic stroke (AIS) admitted to our hospital between 2012-2014 and investigate the effects of a 24-hr stroke thrombolysis emergency treatment on the intrahospital clinical data and outcomes of these patients treated with IV rt-PA thrombolysis. BACKGROUND: Although prenotification of stroke by emergency medical services has been endorsed by the national recommendations and implemented in some developed countries, the development in China is limited. DESIGN: A retrospective, single-centre, observational study. METHODS: Patients with AIS admitted to our hospital between January 2012-December 2014 were included; those who received IV rt-PA thrombolysis within 4.5 hr of onset were investigated. Demographic characteristics, including age and sex, and clinical data and outcomes, including onset-to-treatment time (OTT), door-to-needle time (DNT), premorbid modified Rankin Scale score and proportion of patients treated per year, were all recorded. RESULTS: The proportion of patients with AIS who received thrombolytic therapy within 4.5 hr increased from 2012-2014. The baseline characteristics of all patients were similar. Since the implementation of 24-hr stroke thrombolysis emergency treatment in 2013, the median DNT significantly decreased in 2014 after implementation (42 min) compared with that in 2012 before implementation (81 min) (p < .05). Moreover, the admission-to-imaging time (37 vs. 33 vs. 36 min) and OTT (176 vs. 147 vs. 124 min) significantly decreased during the 3 years (p < .05). CONCLUSIONS: The 24-hr stroke thrombolysis emergency treatment reduced in-hospital delay before thrombolytic therapy but had no effect on the functional outcomes of the patients with AIS. RELEVANCE TO CLINICAL PRACTICE: This study provides opportunities to improve the experiences in using 24-h stroke thrombolysis emergency treatment in patients with AIS in clinical practice.

Calibration of Laser Beam Direction for Inner Diameter Measuring Device.

The laser triangulation method is one of the most advanced methods for large inner diameter measurement. Our research group proposed a kind of inner diameter measuring device that is principally composed of three laser displacement sensors known to be fixed in the same plane measurement position. It is necessary to calibrate the direction of the laser beams that are emitted by laser displacement sensors because they do not meet the theoretical model accurately. For the purpose of calibrating the direction of laser beams, a calibration method and mathematical model were proposed. The inner diameter measuring device is equipped with the spindle of the machine tool. The laser beams rotate and translate in the plane and constitute the rotary rays which are driven to scan the inner surface of the ring gauge. The direction calibration of the laser beams can be completed by the sensors' distance information and corresponding data processing method. The corresponding error sources are analyzed and the validity of the method is verified. After the calibration, the measurement error of the inner diameter measuring device reduced from ± 25 µ m to ± 15 µ m and the relative error was not more than 0.011%.

Cytotoxic activity, apoptosis induction and structure-activity relationship of 8-OR-2-aryl-3,4-dihydroisoquinolin-2-ium salts as promising anticancer agents.

As our continuing research, a series of 2-aryl-8-OR-3,4-dihydroisoquinolin-2-ium bromides were evaluated for cytotoxic activity on cancer cells and apoptosis induction in the present study. SAR was derived also. Among them, 23 compounds showed the higher cytotoxicity on MKN-45 cells with IC50 values of 1.99-11.3µM than a standard anticancer drug cis-platinum (IC50=11.4µM) or their natural model compound chelerythrine (IC50=12.7µM); 16 compounds possessed the medium to high activity on NB4 cells with IC50 values of 1.67-4.62µM. SAR analysis showed that both substitution patterns of the N-aromatic ring and the type of 8-OR significantly impact the activity. AO/EB staining and flow cytometry analysis with Annexin V/PI double staining showed that the compounds were able to induce apoptosis in a concentration-dependent manner. The results above suggested that the title compounds are a class of promising compounds for the development of new anti-cancer drugs.

A Laser-Based Measuring System for Online Quality Control of Car Engine Block.

For online quality control of car engine production, pneumatic measurement instrument plays an unshakeable role in measuring diameters inside engine block because of its portability and high-accuracy. To the limitation of its measuring principle, however, the working space between the pneumatic device and measured surface is too small to require manual operation. This lowers the measuring efficiency and becomes an obstacle to perform automatic measurement. In this article, a high-speed, automatic measuring system is proposed to take the place of pneumatic devices by using a laser-based measuring unit. The measuring unit is considered as a set of several measuring modules, where each of them acts like a single bore gauge and is made of four laser triangulation sensors (LTSs), which are installed on different positions and in opposite directions. The spatial relationship among these LTSs was calibrated before measurements. Sampling points from measured shaft holes can be collected by the measuring unit. A unified mathematical model was established for both calibration and measurement. Based on the established model, the relative pose between the measuring unit and measured workpiece does not impact the measuring accuracy. This frees the measuring unit from accurate positioning or adjustment, and makes it possible to realize fast and automatic measurement. The proposed system and method were finally validated by experiments.

A Fast and in-Situ Measuring Method Using Laser Triangulation Sensors for the Parameters of the Connecting Rod.

The connecting rod is a critical part inside the marine engine. The inspection of its important parameters is directly related to the assembly and quality of the marine engine. A coordinate measuring machine (CMM) is a conventional choice to measure the parameters of a connecting rod. However, CMM requires significant resources in time and cost, which leads researchers into in-situ measurement. This article presents a fast and in-situ measuring method by using a laser-based measuring head. Two measuring strategies are adopted in the inspection process. For positional measurements (such as the hole-center distance), whose accuracy requirement is generally low, the coordinate system of the numerical control (NC) machine is combined with the measuring head to acquire the positional parameters. For dimensional measurements (such as inner diameters), whose accuracy requirement is rather high, the NC machine is used just as transportation. Note that the measuring head has the ability to perform the dimension inspection independently. The accuracy of the measuring head is high enough to meet the dimensional accuracy requirements. Experiments are performed to validate the proposed method. The measuring error of the inner diameters is from 5 µm to 7 µm. The measuring error of hole-center distance is within 15 µm. The measurement of all these parameters can be done within 1 min.

[Clinical utilization of veiled incision and sternocleidomastoid flap in parotidectomy of parotid benign tumors].

PURPOSE: To describe a modified technique of parotidectomy using face-lift approach and sternocleidomastoid flap. METHODS: Forty-six patients were divided into two groups; group 1 (23 cases) using veiled incision and sternocleidomastoid flap, group 2 (23 cases) using traditional incision (Blair's approach) without sternocleidomastoid flap. Postoperative complications included temporary facial paralysis and salivary fistula. The follow-up period was 2 years, oncological recurrence was compared between the two groups. The incidence of Frey's syndrome and the feeling of the region around the auricular lobule were evaluated. The data was analyzed using SPSS10.0 software package with Student's t test and Chi-square test. RESULTS: During the follow up period, the patients in the group 1 showed better aesthetic results than those in the group 2 and without obvious scar and deformity. There was no significant difference between these two groups in temporary facial paralysis, salivary fistula, tumor recurrence, Frey's syndrome, the feeling of the region around the auricular lobule. CONCLUSION: The modified technique of parotidectomy using veiled incision and sternocleidomastoid flap greatly reduces the disadvantages of traditional parotidectomy and provides better aesthetic results.

[A clinical retrospective study on modified parotidectomy in benign tumors of parotid gland].

PURPOSE: A clinical perspective study was designed for patients undergoing a modified parotidectomy to reduce complications of parotidectomy. METHODS: 110 patients were divided randomly into two groups; Group 1 (55 cases) was operated via routine surgical modality. Group 2(55 cases) was treated with preserving the fascia parotideomasseterica and great auricular nerve and partial parotidectomy. Tumor size, blood loss, operating time, temporary facial paralysis, tumour recurrence were compared between the two groups. The follow-up period was 2 years. The incidence of Frey's syndrome was clinically evaluated by Minor test (starch-iodine test). The feeling of the region around the auricular lobule was also evaluated. The data were analyzed using SPSS10.0 software package for Student's t test and Chi-square test. RESULTS: There was no significant difference between the two groups in tumor size, temporary facial paralysis and tumor recurrence. Group 1 was significantly lower than that in Group 2 in the bleeding volume and operating time. The incidence rate of Frey's syndrome in Group 1 was significantly lower than that in Group 2 by objective observation and Minor test. There was significant difference between the feeling of pro- operation and pre-operation in the auricular lobule. CONCLUSIONS: The modified parotidectomy is a function-preserving surgery for benign parotid tumours, which improves the cosmetics, the feeling around ear, reduces the duration of surgery, and the incidence rate of Frey's syndrome. Supported by Research Fund of Science and Technology Bureau of Shanxi Province [Grant No.2005K14-G8(2)] and Science and Technology Project of Xi'an City [Grant No.SF08008-(4)].