Transcription factors TgbHLH95 and TgbZIP44 cotarget terpene biosynthesis gene TgGPPS in Torreya grandis nuts.

Terpenes are volatile compounds responsible for aroma and the postharvest quality of commercially important xiangfei (Torreya grandis) nuts, and there is interest in understanding the regulation of their biosynthesis. Here, a transcriptomics analysis of xiangfei nuts after harvest identified 156 genes associated with the terpenoid metabolic pathway. A geranyl diphosphate (GPP) synthase (TgGPPS) involved in production of the monoterpene precursor GPP was targeted for functional characterization, and its transcript levels positively correlated with terpene levels. Furthermore, transient overexpression of TgGPPS in tobacco (Nicotiana tabacum) leaves or tomato (Solanum lycopersicum) fruit led to monoterpene accumulation. Analysis of differentially expressed transcription factors identified one basic helix-loop-helix protein (TgbHLH95) and one basic leucine zipper protein (TgbZIP44) as potential TgGPPS regulators. TgbHLH95 showed significant transactivation of the TgGPPS promoter, and its transient overexpression in tobacco leaves led to monoterpene accumulation, whereas TgbZIP44 directly bound to an ACGT-containing element in the TgGPPS promoter, as determined by yeast 1-hybrid test and electrophoretic mobility shift assay. Bimolecular fluorescence complementation, firefly luciferase complementation imaging, co-immunoprecipitation, and GST pull-down assays confirmed a direct protein-protein interaction between TgbHLH95 and TgbZIP44 in vivo and in vitro, and in combination these proteins induced the TgGPPS promoter up to 4.7-fold in transactivation assays. These results indicate that a TgbHLH95/TgbZIP44 complex activates the TgGPPS promoter and upregulates terpene biosynthesis in xiangfei nuts after harvest, thereby contributing to its aroma.

Experimental Demonstrations of Alignment and Mode Matching in Optical Cavities with Higher-Order Hermite-Gauss Modes.

Higher-order spatial laser modes have recently been investigated as candidates for reducing test-mass thermal noise in ground-based gravitational-wave detectors such as advanced LIGO. In particular, higher-order Hermite-Gauss (HG) modes have gained attention within the community for their more robust behaviors against random test-mass surface deformations and stronger sensing and control capacities. In this Letter we offer experimental investigations on various aspects of HG mode interferometry. We have generated purified HG modes up to the twelfth order HG_{6,6} mode, with a power conversion efficiency of 38.8% and 27.7% for the HG_{3,3} and HG_{6,6} modes respectively. We demonstrate for the first time the misalignment and mode mismatch-induced power coupling loss measurements for HG modes up to the HG_{6,6}. We report an excellent agreement with the extended numerical power loss factors that in the "small power loss" region converge to 2n+1 or n^{2}+n+1 for a misaligned or mode mismatched HG_{n,n} mode. We also demonstrate the wavefront sensing (WFS) signal measurement for HG modes up to the HG_{6,6}. The measurement result is accurately in accordance with theoretical WFS gain ß_{n,n-1}sqrt[n]+ß_{n,n+1}sqrt[n+1] for an HG_{n,n} mode, with ß_{n,n-1} being the beat coefficient of the adjacent HG_{n,n} and HG_{n-1,n} modes on a split photodetector.

Gas Chromatography-Mass Spectrometry Metabolites and Transcriptome Profiling Reveal Molecular Mechanisms and Differences in Terpene Biosynthesis in Two Torrya grandis Cultivars during Postharvest Ripening.

Terpene aroma compounds are key quality attributes of postharvest Torreya grandis nuts, contributing to their commercial value. However, terpene biosynthesis and regulatory networks in different T. grandis cvs. are still poorly understood. Here, chief cvs. 'Xi Fei' and 'Xiangya Fei' were investigated for their differences in terpene biosynthesis and gene expression levels during postharvest ripening using headspace solid-phase microextraction (HS-SPME) coupled with gas chromatography-mass spectrometry (GC-MS) and transcriptomic datasets. A total of 28 and 22 aroma compounds were identified in 'Xi Fei' and 'Xiangya Fei', respectively. Interestingly, differences in aroma composition between the two cvs. were mostly attributed to D-limonene and α-pinene levels as key determinants in Torreya nuts' flavor. Further, transcriptome profiling, correlation analysis, and RT-qPCR annotated two novel genes, TgTPS1 in 'Xi Fei' and TgTPS2 in 'Xiangya Fei', involved in terpene biosynthesis. In addition, six transcription factors (TFs) with comparable expression patterns to TgTPS1 and four TFs to TgTPS2 were identified via correlation analysis of a volatile and transcriptome dataset to be involved in terpene biosynthesis. Our study provides novel insight into terpene biosynthesis and its regulation at the molecular level in T. grandis nut and presents a valuable reference for metabolic engineering and aroma improvement in this less explored nut.

Cardioprotective effect of NRG-4 gene expression on spontaneous hypertension rats and its mechanism through mediating the activation of ErbB signaling pathway.

To explore the myocardial protective effect of Neuregulin-4 (NRG-4) gene expression on spontaneous hypertension (SHR) rats and its mechanism through mediating the activation of the ErbB signaling pathway, this study was conducted. For this purpose, forty 24-week-old male SPF SHR rats were selected as the experimental group, and 10 age and sex-matched Wistar Kyoto (WKY) rats were selected as the control group. Cardiac tissues were collected for hematoxylin-eosin (HE) staining, terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) staining, Masson staining, and immunohistochemical staining. Following tail vein injection of recombinant lentiviral vectors, the experimental groups were constructed as the control group (SHR rats without any treatment), Empty vector group (Empty Vector transfection), shRNA negative control (NC) group (LV-shRNA-NRG-4 NC transfection to silence the expression of NRG-4), shRNA group (LV-shRNA-NRG-4 transfection), pcDNA3.1(-) NC group (pcDNA3.1(-)-NRG-4 empty vector transfection) and pcDNA3.1(-) group (pcDNA3.1(-)-NRG-4 transfection to overexpress NRG-4). Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot were used to detect the expression levels In addition, methyl thiazolyl tetrazolium salt (MTT) assay and flow cytometry were performed to detect the proliferation and apoptosis of cardiomyocytes, respectively. Results showed that in the SHR group, the cardiomyocytes showed hypertrophy, disordered arrangement, hyperchromatic nucleus, irregular shape, obvious rupture of myocardial fibers, and obvious proliferation of fibrous stroma; obvious myocardial fibrosis, and there were more blue collagen fibers around cardiomyocytes and myocardial arterioles; cardiomyocytes were swollen, muscle fibers arranged disorderly, collagen around the coronary artery and myocardial interstitium increased significantly with a cross-linking appearance; besides, compared with WKY group, the apoptosis index of cardiomyocytes in SHR group was significantly increased (P<0.05). The expression of NRG-4 protein was decreased in the SHR group compared with the WKY group (P<0.05). In vitro, there was no difference in the mRNA expression of NRG-4, ErbB2 and ErbB4, MMP2, TGFß1 and α-SMA, as well as Caspase3, Bax and Bcl-2 among the control group, Empty vector group, shRNA NC group and pcDNA3.1(-) NC group (P>0.05). While shRNA group showed decreased expressions of NRG-4, ErbB2, ErbB4, MMP2, TGFß1, α-SMA and Bcl-2, while increased Caspase3 and Bax expressions, as well as promoted cell proliferation and cell apoptosis when compared with the shRNA NC group (P<0.05); while compared with pcDNA3.1(-) NC group, pcDNA3.1(-) group had highly increased expressions of NRG-4, ErbB2, ErbB4, MMP2, TGFß1, α-SMA and Bcl-2, while decreased Caspase3 and Bax expressions, inhibited cell proliferation and cell apoptosis (all P<0.05). It is concluded Upregulation of NRG-4 gene expression can promote the activation of the ErbB signaling pathway, thus inhibiting the proliferation and apoptosis of cardiomyocytes in SHR rats, reversing myocardial fibrosis, and playing its cardioprotective role.

Correlation analysis between preoperative systemic immune inflammation index and prognosis of patients after radical gastric cancer surgery: based on propensity score matching method.

BACKGROUND: To explore the correlation between the preoperative systemic immune inflammation index (SII) and the prognosis of patients with gastric carcinoma (GC). METHODS: The clinical data of 771 GC patients surgically treated in the Department of Gastrointestinal Surgery, Qinghai University Affiliated Hospital from June 2010 to June 2015 were retrospectively analyzed, and their preoperative SII was calculated. The optimal cut-off value of preoperative SII was determined using the receiver operating characteristic (ROC) curve, the confounding factors between the two groups were eliminated using the propensity score matching (PSM) method, and the correlation between preoperative SII and clinicopathological characteristics was assessed by chi-square test. Moreover, the overall survival was calculated using Kaplan-Meier method, the survival curve was plotted, and log-rank test was performed for the significance analysis between the curves. Univariate and multivariate analyses were also conducted using the Cox proportional hazards model. RESULTS: It was determined by the ROC curve that the optimal cut-off value of preoperative SII was 489.52, based on which 771 GC patients were divided into high SII (H-SII) group and low SII (L-SII) group, followed by PSM in the two groups. The results of Kaplan-Meier analysis showed that before and after PSM, the postoperative 1-, 3-, and 5-year survival rates in L-SII group were superior to those in H-SII group, and the overall survival rate had a statistically significant difference between the two groups (P < 0.05). Before PSM, preoperative SII [hazard ratio (HR) = 2.707, 95% confidence interval (CI) 2.074-3.533, P < 0.001] was an independent risk factor for the prognosis of GC patients. After 1:1 PSM, preoperative SII (HR = 2.669, 95%CI 1.881-3.788, P < 0.001) was still an independent risk factor for the prognosis of GC patients. CONCLUSIONS: Preoperative SII is an independent risk factor for the prognosis of GC patients. The increase in preoperative SII in peripheral blood indicates a worse prognosis.

Power coupling losses for misaligned and mode-mismatched higher-order Hermite-Gauss modes.

This paper analytically and numerically investigates misalignment and mode-mismatch-induced power coupling coefficients and losses as a function of Hermite-Gauss (HG) mode order. We show that higher-order HG modes are more susceptible to beam perturbations when, for example, coupling into optical cavities: the misalignment and mode-mismatch-induced power coupling losses scale linearly and quadratically with respect to the mode indices, respectively. As a result, the mode-mismatch tolerance for the ${{\rm HG}_{3,3}}$ mode is reduced to a factor of 0.28 relative to the currently used ${{\rm HG}_{0,0}}$ mode. This is a potential hurdle to using higher-order modes to reduce thermal noise in future gravitational-wave detectors.

Plant growth-promoting activities of bacterial endophytes isolated from the medicinal plant Pairs polyphylla var. yunnanensis.

Pairs polyphylla var. yunnanensis (Paris L.) is a valuable medicinal plant used in traditional Chinese medicine. The market demand for P. polyphylla has increased over time, but it has slow growth and a low natural propagation rate. Endophytic bacteria are bioactive microorganisms that form a mutualistic relationship with host plants in long-term coordinated evolution, and they can promote the growth and accumulation of effective components in host plants. The aims of this study were to identify endophytic bacteria of P. polyphylla and to characterize their properties in promoting plant growth. A total of 10 endophytic bacteria were isolated from rhizomes of P. polyphylla. The isolated endophytes exhibited a variable capacity for indole acetic acid production, phosphate solubilization and nitrogen fixation. To investigate the effects of the endophytes on plant growth, four endophyte strains, G5, J2, G20, and Y2, were selected to compare their ability to promote plant growth. The results indicated that microbial endophytes isolated from P. polyphylla rhizomes play a vital role in improving P. polyphylla plant growth and could be used as inoculants to establish a sustainable crop production system.

Hesperidin ameliorates insulin resistance by regulating the IRS1-GLUT2 pathway via TLR4 in HepG2 cells.

The aim of this study was to evaluate the effect and mechanism of hesperidin (HES) on insulin resistance (IR) in the human hepatocellular carcinoma cell line (HepG2 cells). HepG2 cells were induced with lipopolysaccharide (LPS) as a model of IR and treated with HES at three dosages. Next, the levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), the glucose content, and glucose uptake were evaluated by enzyme-linked immunosorbent assay, glucose oxidase-peroxidase method (GOD-POD), or (2-(N-(7-nitrobenz-2-oxa-1, 3-diazol-4-yl)amino)-2-deoxyglucose) (2-NBDG). Moreover, the protein expression of toll-like receptors 4 (TLR4), insulin receptor substrate 1 (IRS1), nuclear factor kappa B (NF-κB), and glucose transporter 2 (GLUT2) in HepG2 cells treated with HES were assessed via western blotting analysis. In addition, GLUT2 protein expression exposed to HES was detected following treatment with TLR4 inhibitor (HTA125). Our results demonstrated that HES decreased the levels of TNF-α and IL-6, attenuated the glucose content in culture medium and increased glucose uptake in insulin-resistant HepG2 cells in vitro. Moreover, HES upregulated the expression of IRS1 and GLUT2 protein and downregulated the protein expression of TLR4 and NF-κB in insulin-resistant HepG2 cells. The expression of GLUT2 protein had no significant changes when treated with HES after blockade of TLR4. HES attenuated IR in LPS-inducedinsulin-resistant HepG2 cells. Therefore, regulating the IRS1-GLUT2 pathway via TLR4 represents a potential mechanism of HES on IR in HepG2 cells.

Altered Long Noncoding RNA and Messenger RNA Expression in Experimental Intracerebral Hemorrhage - a Preliminary Study.

BACKGROUND/AIMS: Functional recovery in the chronic phase is a difficult problem in intracerebral hemorrhage (ICH) treatment. Long noncoding RNAs (lncRNAs) are demonstrated to be involved in central nervous system (CNS) disorders. However, the roles of lncRNAs in post-ICH injury and repair are poorly understood, especially those that may be attributed to long-term neurological deficit. The present study depicted the lncRNA and messenger RNA (mRNA) profile by microarray at late stage after an experimental ICH. METHODS: LncRNA and mRNA microarray was used to first identify differentially expressed genes. Gene ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to determine bio-functions and signaling pathways, with which differentially expressed genes are most closely related. Quantitative real-time polymerase chain reaction (PCR) was used to validate the results of microarray. Finally, the lncRNA-mRNA co-expression network was constructed to find the interaction of genes. RESULTS: A total of 625 differentially expressed lncRNAs and 826 expressed mRNAs were identified. Altered genes were enriched in mitochon-drial matrix, G-protein coupled receptor signaling pathway, and olfactory transduction, which may be associated with ICH-induced pathophysiologic changes in the long term. A co-expression network profile based on 5 validated differentially expressed lncRNAs and 205 interacted mRNAs was composed of 210 nodes and 298 connections. CONCLUSION: Mitochondrial matrix, reduced G-protein coupled receptor activity, and impaired olfactory transduction may be involved in the sequelae following ICH. Further, these dysregulated lncRNAs and mRNAs may be the promising therapeutic targets to overcome obstacles in functional recovery following ICH.

Broad-spectrum enhanced absorption of graphene-molybdenum disulfide photovoltaic cells in metal-mirror microcavity.

The optical absorption of graphene-molybdenum disulfide photovoltaic cells (GM-PVc) in wedge-shaped metal-mirror microcavities (w-MMCs) combined with a spectrum-splitting structure was studied. Results showed that the combination of spectrum-splitting structure and w-MMC can enable the light absorption of GM-PVcs to reach about 65% in the broad spectrum. The influence of processing errors on the absorption of GM-PVcs in w-MMCs was 3-14 times lower than that of GM-PVcs in wedge photonic crystal microcavities. The light absorption of GM-PVcs reached 60% in the broad spectrum, even with the processing errors. The proposed structure is easy to implement and may have potentially important applications in the development of ultra-thin and high-efficiency solar cells and optoelectronic devices.

The effect of rotative stress on CAII, FAS, FASL, OSCAR, and TRAP gene expression in osteoclasts.

This study was designed to explore the effects of rotative stress on carbonic anhydrase II (CAII), TNF receptor superfamily member 6 (FAS), FAS ligand (FASL), osteoclast-associated receptor (OSCAR), and tartrate-resistant acid phosphatase (TRAP) gene expression in osteoclasts. Osteoclasts were induced from RAW264.7 cells cultured in medium containing recombinant murine soluble receptor activator of NF-Kß ligand (sRANKL). The mRNA and protein expression of CAII, FAS, FASL, OSCAR, and TRAP genes in osteoclasts was detected by RT-PCR and Western blot, respectively, after osteoclasts were loaded at various rotative stress strengths and times. No significant differences in mRNA and protein expression were observed between any of the control groups (P > 0.05). Importantly, rotative stress had a significant effect on the mRNA and protein expression of these genes (P < 0.05). We found a negative relationship between rotative stress strength and prolonged loading time and the expression of FAS/FASL genes in osteoclasts. In addition, there was a positive relationship between rotative stress strength and prolonged loading time and the expression of CAII, OSCAR, or TRAP genes in osteoclasts. Based on these results, rotative stress has a significant effect on CAII, FAS, FASL, OSCAR, and TRAP gene expression in osteoclasts.

Design and preliminary biomechanical analysis of artificial cervical joint complex.

OBJECTIVE: To design an artificial cervical joint complex (ACJC) prosthesis for non-fusion reconstruction after cervical subtotal corpectomy, and to evaluate the biomechanical stability, preservation of segment movements and influence on adjacent inter-vertebral movements of this prosthesis. METHODS: The prosthesis was composed of three parts: the upper/lower joint head and the middle artificial vertebrae made of Cobalt-Chromium-Molybdenum (Co-Cr-Mo) alloy and polyethylene with a ball-and-socket joint design resembling the multi-axial movement in normal inter-vertebral spaces. Biomechanical tests of intact spine (control), Orion locking plate system and ACJC prosthesis were performed on formalin-fixed cervical spine specimens from 21 healthy cadavers to compare stability, range of motion (ROM) of the surgical segment and ROM of adjacent inter-vertebral spaces. RESULTS: As for stability of the whole lower cervical spine, there was no significant difference of flexion, extension, lateral bending and torsion between intact spine group and ACJC prosthesis group. As for segment movements, difference in flexion, lateral bending or torsion between ACJC prosthesis group and control group was not statistically significant, while ACJC prosthesis group showed an increase in extension (P < 0.05) compared to that of the control group. In addition, ACJC prosthesis group demonstrated better flexion, extension and lateral bending compared to those of Orion plating system group (P < 0.05). Difference in adjacent inter-vertebral ROM of the ACJC prosthesis group was not statistically significant compared to that of the control group. CONCLUSION: After cervical subtotal corpectomy, reconstruction with ACJC prosthesis not only obtained instant stability, but also reserved segment motions effectively, without abnormal gain of mobility at adjacent inter-vertebral spaces.

High-performance sorbents from ionic liquid activated walnut shell carbon: an investigation of adsorption and regeneration.

In this paper, walnut shells were selected to make activated charcoal using ionic activators. Based on the physical/chemical activation process and the properties of activated carbon products, the Fourier Transform Infrared reflection and Brunauer-Emmett-Teller analysis methods were adopted to comparatively analyse activation principles and pore-structure parameters. Also ciprofloxacin adsorption was compared among various activated carbon. Then, an absence of microporous structure in both walnut shells and their carbonized derivatives was found. Moreover, the specific surface area of activated carbon, prepared via KOH wet activation within physical/chemical procedures, attains a noteworthy 1787.06 m2 g-1, underlining its commendable adsorption performance. The specific surface areas of five distinct activated carbons, processed via ionic activation, extend from 1302.01 to 2214.06 m2 g-1. Concurrently, the micropore volumes span from 0.47 to 0.93 cm3 g-1. Obviously, the adsorption proficiency of ion-activated carbon markedly exceeds that of carbons activated physically or chemically. Of all materials investigated in this paper, ion-activated carbon D consistently exhibits superior performance, maintaining a ciprofloxacin removal rate nearing 100% at 40 °C. Remarkably, the maximum regeneration frequency of ion-activated carbons can reach up to 10 cycles. In conclusion, these five ion-activated carbons, demonstrating superior pore-structure parameters and adsorptive capacities, outperform those prepared through physical/chemical methods. They emerge as promising contenders for new, high-performing adsorbents.

Tissue-selecting-technique mega-window stapler combined with anal canal epithelial preservation operation in prolapsed hemorrhoids.

OBJECTIVE: This study aimed to compare the efficiency of these two combined surgeries [prolapse and hemorrhoids (PPH) combined with the external hemorrhoidectomy and inferior internal hemorrhoid ligation; tissue selecting technique with mega-window stapler (TST-MS) combined with anal canal epithelial preservation operation]. METHODS: This is a single-center, evaluator-blinded randomized controlled trial (RCT). A total of 204 participants were randomly divided into the two groups. The anal function, reoccurrence, intraoperative variables, and operative complications were assessed. The measurement data were compared by paired t test and rank sum test. Chi-squared or Fisher's exact test was used for count data and rank sum test for ranked data. To assess differences within each group in different time points, the repeated-measures analysis of variance was conducted. RESULTS: TST-MS combined with anal canal epithelial preservation operation had lower Wexner score of anal incontinence (Z = 3.062, P = 0.002), higher patients' satisfaction degree (t = 7.32, P < 0.001), less residual skin tags (χ2 = 18.141, P < 0.001), longer operative time (Z = -2.281, P = 0.023), and bigger volume of excised rectal mucosa (t = 2.35, P = 0.020). There was no significant difference between the two groups in the anal canal circumference, recurrence, intraoperative blood loss, weight of excised rectal mucosa, anal pain, bleeding, urinary retention, anal edge edema, and anatomical anal stenosis (all P > 0.05). CONCLUSIONS: TST-MS combined with anal canal epithelial preservation operation showed better clinical efficiency in the treatment of prolapsed hemorrhoids. TRIAL REGISTRATION: This study has been registered in Chinese Clinical Trial Registry (ChiCTR2000038533).

Optimization of underground open intermediary space comfort in TOD complexes: A case study of Chongqing, China.

Rapid urbanization drives social development, but at the same time brings sustainable development Rapid urbanization drives social development, but at the same time brings sustainable development advantages of expanding underground space and relieving urban traffic congestion. High quality TOD complexes with natural elements in the intermediary space have been considered as one of the important means to address sustainable urban development. Nevertheless, intermediary spaces in TOD complexes face various challenges, such as significant contradictory factors in their physical environment spaces. This study classifies the underground open intermediary space into four types according to the characteristics of TOD complexes. And for these four types'Cthe physical environment-generated by various influencing factors of planar geometric, three-dimensional geometric, and detailed construction elements-is simulated using a numerical simulation method based on a static Taguchi experiment. The results demonstrate that space shape is a primary influencing factor for luminous and thermal environments; the window-atrium ratio (W/A ratio) and hole-atrium ratio (H/A ratio) comprise contradictory factors between the luminous and thermal environments of these spaces; profile inclination angle and sunken plaza height are primary impact factors for the acoustic environment; and skylight type has minimal influence on the physical environment. On average, their luminous and acoustic environment comfort can be improved by 200%; whereas, their thermal environment comfort can be improved by 21% and the potential for optimizing it in their shallow space (underground space depth ≤ 10 m) is relatively low. Subsequently, the necessity of comfort optimization as the passive optimization design of underground open intermediary spaces' physical environment in TOD complexes in the future is discussed. Finally, the feasible path and prospect of how to improve the livability and comfort of the spatial physical environment of TOD complexes are discussed and prospected.

Qiteng Xiaozhuo granules medicated serum inhibits excessive proliferation and promotes apoptosis of human glomerular mesangial cells by targeting fat mass and obesity associated proteins.

OBJECTIVE: To explore whether fat mass and obesity associated proteins (FTO) is an important target of Qiteng Xiaozhuo granules (QTXZG,) medicated serum in regulating proliferation and apoptosis of glomerular mesangial cells. METHODS: Medicated serum was obtained from Sprague-Dawley (SD) rats administered intragastrically with QTXZG decoction. The optimal concentration and intervention time of medicated serum were selected with the cell counting kit 8 assay. Cell proliferation was assessed by 5-ethynyl-2'-deoxyuridine (EdU) and cell apoptosis was investigated using flow cytometry. The expression of FTO, Proliferating cell nuclear antigen, Cyclin D1, B-cell lymphoma 2 (Bcl2) and BCL2 assaciated X was detected by Western blot and Real-time quantitative polymerase chain reaction, respectively. Quantification of the m6A RNA methylation was utilized to determine the total level of m6A methylation modification. RESULTS: EdU and flow cytometry assays revealed that QTXZG medicated serum can remarkably inhibit proliferation and promote apoptosis of lipopolysaccharide (LPS)-induced human glomerular mesangial cells (HGMCs). The FTO overexpression plasmid could inhibit proliferation and promote apoptosis of LPS-induced HGMCs. The FTO inhibitor (FB23-2) can significantly attenuate the effect of QTZXG medicated serum on inhibiting excessive proliferation and promoting apoptosis. QTXZG medicated serum can significantly increase FTO expression and decrease the level of m6A methylation modification. CONCLUSIONS: FTO is a key target for QTXZG medicated serum in inhibiting excessive proliferation and promoting apoptosis of human glomerular mesangial cells.

A Hybrid Two-Stage Teaching-Learning-Based Optimization Algorithm for Feature Selection in Bioinformatics.

The "curse of dimensionality" brings new challenges to the feature selection (FS) problem, especially in bioinformatics filed. In this paper, we propose a hybrid Two-Stage Teaching-Learning-Based Optimization (TS-TLBO) algorithm to improve the performance of bioinformatics data classification. In the selection reduction stage, potentially informative features, as well as noisy features, are selected to effectively reduce the search space. In the following comparative self-learning stage, the teacher and the worst student with self-learning evolve together based on the duality of the FS problems to enhance the exploitation capabilities. In addition, an opposition-based learning strategy is utilized to generate initial solutions to rapidly improve the quality of the solutions. We further develop a self-adaptive mutation mechanism to improve the search performance by dynamically adjusting the mutation rate according to the teacher's convergence ability. Moreover, we integrate a differential evolutionary method with TLBO to boost the exploration ability of our algorithm. We conduct comparative experiments on 31 public data sets with different data dimensions, including 7 bioinformatics datasets, and evaluate our TS-TLBO algorithm compared with 11 related methods. The experimental results show that the TS-TLBO algorithm obtains a good feature subset with better classification performance, and indicates its generality to the FS problems.

Efficacy of press needle on immune function and quality of life in female breast cancer patients after radical mastectomy: study protocol for a randomized controlled trial.

Radical mastectomy may lead to suppression of cellular immune function in patients with malignant tumors, and affect the quality of life (QOL) of patients. Immune suppression is a common cause of complications and adverse reactions in adjuvant therapy after radical mastectomy of breast cancer. Currently, there are few proven effective treatments for immune suppression. Therefore, it's necessary to develop a new treatment method. Press needle is widely used in clinical practice. However, there have been relatively few studies that evaluate the effects of press needle on postoperative immune function. The aim of the present study is to assess the effects of press needle on immune function and QOL in female breast cancer patients undergoing radical mastectomy. This study will be a single-center, randomized and single-blinded trial. Totally 78 eligible patients will be randomized in a ratio of 1:1 to the press needle group or the sham press needle group. During the treatment phase, patients will undergo five times weekly of verum press needle or sham press needle for 2 weeks. The primary outcome measures will be the peripheral blood levels of CD8+, CD4+, CD3+, and CD4+/CD8+ T cells. The secondary outcome measures will be the changes of patients' QOL, evaluated by the Karnofsky Performance Scale score and the EORTC core quality of life questionnaire (EORTC QLQ-C30). Furthermore, 5-year survival rate and recurrence rate will be evaluated. Safety and adverse events will be assessed at each visit. The results of this on-going study will provide clinical evidence for the effects and safety of press needle on immune function and QOL in patients after breast cancer resection compared with sham press needle. Trial registration: Chinese Clinical Trial Registry, ChiCTR2000040100. Registered on 21 November 2020.

Ethylene treatment promotes umami taste-active amino acids accumulation of Torreya grandis nuts post-harvest by comparative chemical and transcript analyses.

Amino acids play critical roles in physiological processes and also contribute significantly to fruit quality. In this study, the effect of exogenous ethylene on amino acids metabolism and related genes expression in Torreya grandis were investigated. The results revealed that ethylene treatment (3000 µL L-1 for 24 h) significantly increased amino acids level. Umami amino acids were distinctly upregulated in ethylene-treated versus control nuts, with glutamic and aspartic acids to demonstrate 1.9-fold and 2.1-fold increase. Transcriptome analysis revealed that deferentially expressed genes were mainly enriched in alanine aspartate and glutamate metabolism. RT-qPCR confirmed that ethylene treatment up-regulated expression of their biosynthesis genes (TgGOGAT1, TgAATC1, TgAATC4) concurrent with suppression of their degradation enzymes (TgGS2, TgGAD1, TgGAD3, TgASNS1). Ethylene treatment appears to promote umami taste-active amino acids and improve T. grandis nut quality post-harvest.

mTORC1-Dependent and GSDMD-Mediated Pyroptosis in Developmental Sevoflurane Neurotoxicity.

Developmental sevoflurane exposure leads to neuronal cell death, and subsequent learning and memory cognitive defects. The underlyi\ng mechanism remains to be elucidated. Gasdermin D (GSDMD)-mediated pyroptosis is a form of inflammatory cell death and participates in a variety of neurodegenerative diseases. Several studies illustrated that dysregulation of mTOR activity is involved in pyroptotic cell death. The current study was designed to interrogate the role of GSDMD-mediated pyroptosis and mTOR activity in developmental sevoflurane exposure. We found that inhibition of GSDMD pore formation with Disulfiram (DSF) or Necrosulfonamide (NSA) significantly attenuated sevoflurane neurotoxicity in vitro. In addition, treatment with DSF or NSA also mitigated damage-associated molecular patterns (DAMPs) release and subsequent plasma membrane rupture (PMR) induced by sevoflurane challenge. Further investigation showed that the overactivation of mTOR signaling is involved in sevoflurane induced pyroptosis both in vivo and in vitro. Intriguingly, we found that the DAMPs release and subsequent PMR triggered by developmental sevoflurane priming were compromised by knocking down the expression of mTORC1 component Raptor, but not mTORC2 component Rictor. Moreover, sevoflurane induced pyroptosis could also be restored by suppressing mTOR activity or knocking down the expressions of Ras-related small GTPases RagA or RagC. Finally, administration of DSF or NSA dramatically improved the spatial and emotional cognitive disorders without alternation of locomotor activity. Taken together, these results indicate that mTORC1-dependent and GSDMD-mediated pyroptosis contributes to the developmental sevoflurane neurotoxicity. Characterizing these processes may provide experimental evidence for the possible prevention of developmental sevoflurane neurotoxicity.