Amygdala dynorphin/κ opioid receptor system modulates depressive-like behavior in mice following chronic social defeat stress.

Major depression disorder is a severe and recurrent neuropsychological disorder characterized by lowered mood and social activity and cognitive impairment. Owing to unclear molecular mechanisms of depression, limited interventions are available in clinic. In this study we investigated the role of dynorphin/κ opioid receptor system in the development of depression. Mice were subjected to chronic social defeat stress for 14 days. Chronic social defeat stress induced significant social avoidance in mice characterized by decreased time duration in the interaction zone and increased time duration in the corner zone. Pre-administration of a κ opioid receptor antagonist norBNI (10 mg/kg, i.p.) could prevent the development of social avoidance induced by chronic social defeat stress. Social avoidance was not observed in κ opioid receptor knockout mice subjected to chronic social defeat stress. We further revealed that social defeat stress activated c-fos and ERK signaling in the amygdala without affecting the NAc, hippocampus and hypothalamus, and ERK activation was blocked by systemic injection of norBNI. Finally, the expression of dynorphin A, the endogenous ligand of κ opioid receptor, was significantly increased in the amygdala following social defeat stress; microinjection of norBNI into the amygdala prevented the development of depressive-like behaviors caused by social defeat stress. The present study demonstrates that upregulated dynorphin/κ opioid receptor system in the amygdala leads to the emergence of depression following chronic social defeat stress, and sheds light on κ opioid receptor antagonists as potential therapeutic agents for the prevention and treatment of depression following chronic stress.

[Mechanism of gambogenic acid in resisting angiogenesis of lung cancer in vitro].

The aim of this paper was to observe the effect of gambogenic acid on angiogenesis of lung cancer and its preliminary mechanism. After culturing lung adenocarcinoma A549 cells, the conditioned medium was treated with gambogenic acid and then used to culture human umbilical vein endothelial cells (HUVECs) to establish the indirect contact cell co-culture system. A two-dimensional culture model of HUVEC was established with matrigel to observe the effect of gambogenic acid on angiogenesis. DAPI staining was used to observe the morphological changes in HUVEC cells after treatment with gambogenic acid under the fluorescence microscope. Annexin V-FITC/PI staining and flow cytometry analysis were used to determine gambogenic acid's effect on HUVEC cell apoptosis rate. The protein expressions of PI3K, p-PI3K, Akt, p-Akt were measured by Western blot. PTEN-siRNA was transfected into cells, and RT-PCR was used to detect the expression levels of PI3K and Akt genes. Gambogenic acid can significantly inhibit angiogenesis, and its inhibitory effect was dose-dependent. DAPI staining showed apoptotic morphological features of HUVEC cells under fluorescence microscope. Annexin V-FITC/PI staining showed that gambogenic acid induced apoptosis in HUVECs. The results of Western blot showed that the expressions of p-PI3K and p-Akt protein were down-regulated with gambogenic acid, while the expressions of PI3K and Akt protein was insignificant. The results of RT-PCR indicated that the expressions of PI3K and Akt protein were up-regulated by PTEN siRNA. Gambogenic acid can inhibit angiogenesis in lung cancer in vitro, and the mechanism of inhibiting angiogenesis may be related to the PI3K/Akt signaling pathway.

Development of neural basis for chinese orthographic neighborhood size effect.

The brain activity of orthographic neighborhood size (N size) effect in Chinese character naming has been studied in adults, meanwhile behavioral studies have revealed a developmental trend of Chinese N-size effect in developing readers. However, it is unclear whether and how the neural mechanism of N-size effect changes in Chinese children along with development. Here we address this issue using functional magnetic resonance imaging. Forty-four students from the 3(rd) , 5(th) , and 7(th) grades were scanned during silent naming of Chinese characters. After scanning, all participants took part in an overt naming test outside the scanner, and results of the naming task showed that the 3(rd) graders named characters from large neighborhoods faster than those from small neighborhoods, revealing a facilitatory N-size effect; the 5(th) graders showed null N-size effect while the 7(th) graders showed an inhibitory N-size effect. Neuroimaging results revealed that only the 3(rd) graders exhibited a significant N-size effect in the left middle occipital activity, with greater activation for large N-size characters. Results of 5(th) and 7(th) graders showed significant N-size effects in the left middle frontal gyrus, in which 5(th) graders induced greater activation in large N-size condition than in small N-size condition, while 7(th) graders exhibited an opposite effect which was similar to the adult pattern reported in a previous study. The current findings suggested the transition from broadly tuned to finely tuned orthographic representation with reading development, and the inhibition from neighbors' phonology for higher graders. Hum Brain Mapp 37:632-647, 2016. © 2015 Wiley Periodicals, Inc.

[Effects of Huoxue Dingxuan Capsule Glare on Vertebral Artery Blood Flow,Plasma PAI and t-PA in CSA Rat Models.]

OBJECTIVES: To determine the effects of Huoxue Dingxuan Capsule on vertebral artery blood flow,plasma plasminogen activator (t-PA) and plasminogen activator inhibitor (PAI) in rats with cervical spondylosis of vertebral artery type (CSA). METHODS: Ninety healthy male Wistar rats were equally and randomly divided into control,model and treatment groups.The rats in the model and treatment groups were subject to composite modeling manufacturing CSA.The treatment group was given six-week interventions with Huoxue Dingxuan capsule 4 weeks after the modeling.Vertebral artery blood flow,plasma PAI,and t-PA contents were detected before modeling,prior to the interventions,and post interventions. RESULTS: Before the interventions,the rats in the model and treatment groups had significantly lower blood flow of vertebral artery than the controls (P<0.05).The model rats also had increased serum PAI and t-PA contents (P<0.01).After the interventions,significantly higher vertebral blood flow was found in the treatment group compared with the controls (P<0.05).After the interventions,increased serum PAI and t-PA contents were observed in the rats in the model group (P<0.01);whereas,decreased serum PAI and t-PA contents were observed in the rats in the treatment group (P<0.01).The treatment group had lower levels of serum PAI and t-PA contents than the model group (P<0.01). CONCLUSIONS: Huoxue Dingxuan Capsule glare can improve the blood flow of vertebral artery and reduce serum PAI and t-PA contents.

[Study on the polarized reflectance-hyperspectral information fusion technology of tomato leaves nutrient diagnoses].

With 25%, 50%, 75%, 100% and 150%, five levels of, nitrogen (N), phosphorus (P) and potassium (K) nutrition stress samples cultivated in Venlo type greenhouse soilless cultivation mode as the research object, polarized reflectance spectra and hyperspectral images of different nutrient deficiency greenhouse tomato leaves were acquired by using polarized reflectance spectroscopy system developed by our own research group and hyperspectral imaging system respectively. The relationship between a certain number of changes in the bump and texture of non-smooth surface of the nutrient stress leaf and the level of polarization reflected radiation was clarified by scanning electron microscopy (SEM). On the one hand, the polarization spectrum was converted into the degree of polarization through Stokes equation, and the four polarization characteristics between the polarization spectroscopy and reference measurement values of N, P and K respectively were extracted. On the other hand, the four characteristic wavelengths of N, P, K hyperspectral image data were determined respectively through the principal component analysis, followed by eight hyperspectral texture features extracted corresponding to the four characteristic wavelengths through correlation analysis. Polarization characteristics and hyperspectral texture features combined with each characteristics of N, P, K were extracted. These 12 characteristic variables were normalized by maximum-minimum value method. N, P, K nutrient levels quantitative diagnostic models were established by SVR. Results of models are as follows: the correlation coefficient of nitrogen r = 0.961 8, root mean square error RMSE= 0.451; correlation coefficient of phosphorus r = 0.916 3, root mean square error RMSE = 0.620; correlation coefficient of potassium r = 0.940 6, root mean square error RMSE = 0.494. The results show that high precision tomato leaves nutrition prediction model could be built by using polarized reflectance spectroscopy combined with high spectral information fusion technology and achieve good diagnoses effect. It has a great significance for the improvement of model accuracy and the development of special instruments. The research provides a new idea for the rapid detection of tomato nutrient content.

[Effect of chaperone-mediated autophagy in MPP(+) -induced SH-SY5Y cells and interventional effect of puerarin].

OBJECTIVE: To study the protective effect of puerarin on MPP(+) -induced SH-SY5Y cells by chaperone-mediated autophagy (CMA). METHOD: The Parkinson's disease cell model was established by injuring SH-SY5Y cells with 1 mmol x L(-1) MPP+. The CCK-8 staining was adopted to detect the effect the puerarin of different concentrations on the survival rate of MPP(+)-induced SH-SYSY cells. The autophagosome formation was observed under transmission electron microscope. The AO staining showed the changes in the lysosome activity. RT-PCR was used to detect the changes in Lamp2a and Hsc70 mRNA expressions. The western blotting was adopted to test the expressions of Lamp2a, Hsc70 and alpha-synuclein protein in cells. RESULT: Within the concentration range of 12. 5-50.0 micromol x L(-1), the pretreatment with puerain for 30 minutes could protect the injury of MPP+ in SH-SY5Y cells, and showed a certain dose-effect relationship. The AO staining and electron microscope showed the effect of puerain within the concentration range of 12.5-50.0 micromol x L(-1) on 1 mmol x L(-1) MPP(+)-induced SH-SY5Y cells; autophagosomes emerged in cells, and increased along with the rise in the puerarin dose. The results of the flow cytometry revealed that 50.0 micromol x L(-1) of puerarin could protect against the increase of the ROS level in 1 mmol x L(-1) MPP(+) -induced SH-SY5Y cells and prevent the oxidative injury. The results of RT-PCR and western blotting indicated that puerain within the concentration range of 12.5-50.0 micromol x L(-1) alleviated the MPP(+)-induced SH-SY5Y cell injury, and inhibited the accumulation of alpha-synuclein proteins in MPP(+) -induced SH-SY5Y cells by up-regulating Hsc70, Lamp2a mRNA and protein level. CONCLUSION: Puerarin could protect against the MPP(+) -induced cell injury, whose protective mechanism may be related to the chaperone-mediated autophagy pathway of interventional molecules.

[Study of gambogenic acid-induced apoptosis of melanoma B16 cells through PI3K/Akt/mTOR signaling pathways].

OBJECTIVE: To discuss the mechanism of gambogenic acid (GNA) in inducing the apoptosis of melanoma B16 cells. METHOD: The inhibitory effect of GNA on the proliferation of B16 cells was measured by the methyl thiazolyl tetrazolium (MTT) assay. The effect of GNA on B16 cells was detected by the Hoechst 33258 staining. The transmission electron microscopy was used to observe the ultra-structure changes of B16 cells. The changes in PI3K, p-PI3K, Akt, p-Akt, p-mTOR, PTEN proteins were detected by the Western blotting to discuss the molecular mechanism of GNA in inducing the apoptosis of B16 cells. RESULT: GNA showed a significant inhibitory effect in the growth and proliferation of melanoma B16 cells. The cell viability remarkably decreased with the increase of GNA concentration and the extension of the action time. The results of the Hoechst 33258 staining showed that cells processed with GNA demonstrated apparent apoptotic characteristics. Under the transmission electron microscope, B16 cells, after being treated with GNA, showed obvious morphological changes of apoptosis. The Western blot showed a time-dependent reduction in the p-PI3K and p-Akt protein expressions, with no change in p-PI3K and p-Akt protein expression quantities. The p-mTOR protein expression decreased with the extension of time, where as the PTEN protein expression showed a time-dependent increase. CONCLUSION: GNA could inhibit the proliferation of melanoma B16 cells and induce their apoptosis within certain time and concentration ranges. Its mechanism in inducing the cell apoptosis may be related to PI3K/Akt/mTOR signaling pathways.

[Gambogenic acid induces mitochondria-dependent apoptosis in human gastric carcinoma cell line].

OBJECTIVE: To study the effects of Gambogenic acid (GNA) on the growth of human gastric carcinoma cell line MGC-803 and its underlying mechanisms. METHODS: MTT assay was used to measure the cell viability. Apoptosis, mitochondrial membrane potential (MMP), reactive oxygen species (ROS) were detected using flow cytometry method. Among them, Annexin V-FITC/PI double staining was employed in the analysis of apoptosis, Rh123 in analyzing MMP and H2DCFDA in analyzing ROS formation. P53 expression was confirmed by Western blot. RESULTS: 4.0 micromol/L GNA inhibited MGC-803 cells growth in a time dependent manner from 24 to 48 h. At the concentration range from 1.0 to 12.0 micromol/L, the inhibitory effect was in a concentration dependent manner. After treatment with 4.0 micromol/L GNA for 48 h, apoptosis was obviously observed as assayed by Annexin V-FITC/PI staining. Importantly, MMP was decreased and ROS formation was increased following GNA treatment. Additionally, P53 expression was up-regulated following 4.0 micromol/ L GNA treatment in a time dependent manner. CONCLUSION: GNA induces mitochondria-dependent apoptosis and increases P53 expression in human gastric carcinoma cell line.

[Apoptosis of melanoma B16 cells induced by gambogenic acid].

OBJECTIVE: To study the inhibitory effect of Gambogenic acid (GNA) on melanoma B16 cells proliferation, and to explore the role of cell apoptosis. METHODS: The inhibitory effect of GNA on the proliferation of B16 cells was measured by methyl thiazolyl tetrazolium (MTT) assay; Alternation of B16 cells ultrastructure was detected by AO/EB staining under fluorescent microscope; Flow cytometry was used to detect intracellular reactive oxygen species (ROS) in B16 cells generated by GNA treatment Western blotting was used to investigate the expression of intracellular Caspase-3 proteins changes. RESULTS: MTT results showed that the GNA within a certain time and a certain concentration significantly suppressed the proliferation of B16 cells and morphological changes were observed by fluorescence microscope on B16 cells after GNA treatment. AO/EB staining showed that the major cell density decreased. GNA treated cells showed obvious apoptotic status. After the cells treated with GNA, in a short period of time, intracellular ROS levels increased dramatically compared with the control group (P < 0.01), and the mitochondrial membrane had a low potential consistently. Western blotting results showed that changes of intracellular proteins expression in the release of Caspase-3 proteins expression levels were increased after GNA treatment. CONCLUSION: GNA can inhibit malignant melanoma B16 cells growth and proliferation and induce apoptosis within a certain time and at a certain concentration.

Will partial splenic embolization followed by splenectomy increase intraoperative bleeding?

BACKGROUND: Partial splenic embolization (PSE) has been suggested as an alternative to splenectomy in the treatment of hypersplenism. However, some patients may experience recurrence of hypersplenism after PSE and require splenectomy. Currently, there is a lack of evidence-based medical support regarding whether preoperative PSE followed by splenectomy can reduce the incidence of complications. AIM: To investigate the safety and therapeutic efficacy of preoperative PSE followed by splenectomy in patients with cirrhosis and hypersplenism. METHODS: Between January 2010 and December 2021, 321 consecutive patients with cirrhosis and hypersplenism underwent splenectomy at our department. Based on whether PSE was performed prior to splenectomy, the patients were divided into two groups: PSE group (n = 40) and non-PSE group (n = 281). Patient characteristics, postoperative complications, and follow-up data were compared between groups. Propensity score matching (PSM) was conducted, and univariable and multivariable analyses were used to establish a nomogram predictive model for intraoperative bleeding (IB). The receiver operating characteristic curve, Hosmer-Lemeshow goodness-of-fit test, and decision curve analysis (DCA) were employed to evaluate the differentiation, calibration, and clinical performance of the model. RESULTS: After PSM, the non-PSE group showed significant reductions in hospital stay, intraoperative blood loss, and operation time (all P = 0.00). Multivariate analysis revealed that spleen length, portal vein diameter, splenic vein diameter, and history of PSE were independent predictive factors for IB. A nomogram predictive model of IB was constructed, and DCA demonstrated the clinical utility of this model. Both groups exhibited similar results in terms of overall survival during the follow-up period. CONCLUSION: Preoperative PSE followed by splenectomy may increase the incidence of IB and a nomogram-based prediction model can predict the occurrence of IB.

Characterization and expression analysis of seven lipid metabolism-related genes in yellow catfish Pelteobagrus fulvidraco fed high fat and bile acid diet.

SREBPs, such as SREBP1 and SREBP2, were the key transcriptional factors regulating lipid metabolism. The processing of SREBPs involved many genes, such as scap, s1p, s2p, cideb. Here, we deciphered the full-length cDNA sequences of scap, srebp1, srebp2, s1p, s2p, cideb and cidec from yellow catfish Pelteobagrus fulvidraco. Their full-length cDNA sequences ranged from 1587 to 3884 bp, and their ORF length from 1191 to 2979 bp, encoding 396-992 amino acids. Some conservative domains were predicted, including the multiple transmembrane domains in SCAP, the bHLH-ZIP domain in SREBP1 and SREBP2, the ApoB binding region, ER targeting region and LD targeting region in CIDEb, the LD targeting region in the CIDEc, the conserved catalytic site and processing site in S1P, and the transmembrane helix domain in S2P. Their mRNA expression could be observed in the heart, spleen, liver, kidney, brain, muscle, intestine and adipose, but varied with tissues. The changes of their mRNA expression in responses to high-fat (HFD) and bile acid (BA) diets were also investigated in the brain, heart, intestine, kidney and spleen tissues. In the brain, HFD significantly increased the mRNA expression of seven genes (scap, srebp1, srebp2, s1p, s2p, cideb and cidec), and the BA attenuated the increase of scap, srebp1, srebp2, s1p, s2p, cideb and cidec mRNA expression induced by HFD. In the heart, HFD significantly increased the mRNA abundances of six genes (srebp1, srebp2, scap, s2p, cideb and cidec), and BA attenuated the increase of their mRNA abundances induced by HFD. In the intestine, HFD increased the cideb, s1p and s2p mRNA abundances, and BA attenuated the HFD-induced increment of their mRNA abundances. In the kidney, HFD significantly increased the scap, cidec and s1p mRNA expression, and BA diet attenuated the increment of their mRNA expression. In the spleen, HFD treatment increased the scap, srebp2, s1p and s2p mRNA expression, and BA diet attenuated HFD-induced increment of their mRNA expression. Taken together, our study elucidated the characterization, expression profiles and transcriptional response of seven lipid metabolic genes, which would serve as the good basis for the further exploration into their function and regulatory mechanism in fish.

Qingfei mixture modulates the immune responses in lung cancer through modulating mTOR signaling and gut microbiota-derived short-chain fatty acids.

Lung cancer ranks among the primary contributors to cancer-related fatalities on a global scale. Multiple research investigations have demonstrated that there exists a dysbiosis within the intestinal bacteria and short-chain fatty acids (SCFAs) is linked with immune responses in lung cancer. Qingfei mixture (QFM) has been widely used in treating lung cancer, yet the active ingredients and roles of the QFM on immune responses by targeting gut microbiota remain to be elucidated. The chemical constituents of QFM were qualitatively examined by UPLC/Q-TOF-MS. Additionally, we evaluated the therapeutic impact of the organic substance QFM on lung cancer, aiming to elucidate its mechanisms for improving the tumor-immune microenvironment. Herein, we constructed a Lewis lung carcinoma (LLC)-bearing mice model with QFM treatment to observe tumor growth and immune cell changes. Then, the feces were collected and a combinatory study using metagenomes, non-targeted metabonomics, and targeted metabonomics of SCFAs was performed. In vitro experiments have been conducted to estimate the roles of acetate and sodium propionate in CD8+ T cells. Furthermore, we treated tumor-bearing mice with QFM, QFM + MHY1485 (an mTOR activator), and QFM + an antibiotic mixture (ABX) to explore the potential therapeutic benefit of regulation of the tumor microenvironment. A total of 96 compounds were obtained from QFM by UPLC/Q-TOF-MS. Besides, the findings demonstrated that QFM exhibited significant efficacy against lung cancer, manifesting in reduced tumor growth and improved immune responses. In investigating its mechanisms, we integrated gut microbiota sequencing and fecal metabolomics, revealing that QFM effectively restored disruptions in gut microbiota and SCFAs in mice with lung cancer. QFM, acetate, or sodium propionate contributed to the up-regulation of IFN-γ, Gzms-B, perforin, IL-17, IL-6, IL-12, TNF-α expressions and decreased HDAC and IL-10 levels in vitro and in vivo. Moreover, MHY1485 and ABX weakened the effects of QFM on immunomodulation. Collectively, these results suggest that QFM may facilitate immune responses in the LLC-bearing mice via regulating the gut microbiota-derived SCFAs at least partially through targeting the mTOR signaling pathway.

[Risk factors and short-term prognosis of acute kidney injury in elderly patients].

OBJECTIVE: To explore the risk factors and short-term outcomes of acute kidney injury (AKI) in elderly patients. METHODS: A total of 232 elderly AKI patients at Chinese PLA General Hospital from June 2008 to December 2009 were enrolled. They were divided into two groups according to their outcomes at 28 days and at 29 days to 3 months after AKI respectively. Their clinical data were analyzed to explore the risk factors and their effects on the outcomes of AKI. RESULTS: There were 215 males and 17 females with an average age of (86.7 ± 5.3) years. Thirty-eight cases (16.4%) died within 28 days after AKI and 57 (24.6%) died within 3 months. Infection (43.1%) was the major cause of AKI. The other causes included hypovolemia (19.0%), use of nephrotoxic drugs (16.8%) and cardiovascular events (15.1%) respectively. Logistic regression analysis revealed that low body mass index (BMI), oliguria, mechanical ventilation, hypoalbuminemia and peak serum level of creatinine (Scr >246.5 µmol/L) were the prognostic factors of AKI in those patients dying within 28 days after AKI (P < 0.05). Low BMI, hypoalbuminemia and high blood level of urea nitrogen (BUN) were the prognostic factors of AKI in those patients dying within 29 days to 3 months after AKI (P < 0.05). CONCLUSION: Infection, hypovolemia, use of nephrotoxic drugs and cardiovascular events are common causes of AKI in elderly patients.Low BMI, oliguria, mechanical ventilation, hypoalbuminemia, high level of BUN and peak level of Scr ( > 246.5 µmol/L) are the prognostic factors of AKI in elderly patients.

[Effect and mechanism of polyphyllin I on human cervical cancer cell HeLa in vitro].

OBJECTIVE: To study the effect and mechanism of polyphyllin I on human cervical cancer cell HeLa. METHODS: The cell growth and proliferation effect of Polyphyllin I on HeLa cells were measured by MTT assay; Hoechst 33258 fluorescent staining was used to record changes in cell morphology and morphological changes in mitochondria of Polyphyllin I before and after treatment on He La cells. Annexin V-FITC/PI staining was used to detect the ratio of tumor cell apoptosis by flow cytometry. Release of intracellular re active oxygen species (ROS) generation level in HeLa cells was determined by flow cytometry,Caspase-3 activity was measured by fluorescent assay kits. RESULTS: MTT results showed that Polyphyllin I could significantly suppressed the proliferation of HeLa cells and in time-and concentration-dependence manner. The intracellular ROS levels were increased dramatically and the mitochondrial membrane was decreased consistently. Caspase-3 proteins expression levels were increased after Polyphyllin I treatment. CONCLUSION: Polyphyllin I could inhibit HeLa cells growth and proliferation and its mechanism may be related to inducing cell apoptosis.

Fatigue as a Cause of Professional Dissatisfaction Among Chinese Nurses in Intensive Care Unit During COVID-19 Pandemic.

Aim: To clarify the mediating role of burnout and the moderating role of turnover intention in the association between fatigue and job satisfaction among Chinese nurses in intensive care units (ICU) during the COVID-19 pandemic. Methods: A cross-sectional survey of fifteen provinces in China was conducted, using an online questionnaire, from December 2020 to January 2021, during the COVID-19 pandemic. A total of 374 ICU nurses (effective response rate: 71.37%) provided sufficient responses. Sociodemographic factors, job demographic factors, fatigue, burnout, job satisfaction, and turnover intention were assessed using questionnaires. General linear modeling (GLM), hierarchical linear regression (HLR) analysis, and generalized additive modeling (GAM) were performed to examine all the considered research hypotheses. Results: Fatigue was found to be negatively and significantly associated with job satisfaction. Moreover, burnout played a partial mediating role and turnover intention played a moderating role in the relationship between fatigue and job satisfaction. Conclusion: Over time, a state of physical and mental exhaustion and work weariness among Chinese ICU nurses potentially results in job burnout and consequently promotes the level of job dissatisfaction. The results also found that turnover intention played a moderating role in the relationship between burnout and job satisfaction. Specific policies could be considered to eliminate nurses' fatigue and negative attitudes during times of public health emergencies.

Neural basis of phonological processing in second language reading: an fMRI study of Chinese regularity effect.

The present study examined the neural basis of phonological processing in Chinese later acquired as a second language (L2). The regularity effect of Chinese was selected to elucidate the addressed phonological processing. We recruited a group of alphabetic language speakers who had been learning Chinese as L2 for at least one year, and a control group of native Chinese speakers. Participants from both groups exhibited a regularity effect in a pilot behavioral test. Neuroimaging results revealed that L2 learners exhibited stronger activation than native Chinese speakers in the right occipitotemporal region (i.e. right lingual gyrus and right fusiform gyrus). Moreover, L2 learners exhibited greater activations in the ventral aspects of the left inferior parietal lobule (LIPL) and the left inferior frontal gyrus (LIFG) for irregular character reading minus regular character reading. In contrast, native Chinese speakers exhibited more dorsal activations in the LIPL and LIFG. According to the "accommodation/assimilation" hypothesis of second language reading, the current findings suggest that native speakers of alphabetic languages utilized an accommodation pattern for the specific requirements of the visual form of Chinese characters, and an assimilation pattern for orthography-to-phonology transformation in Chinese reading.

Integrated microbiome, metabolome, and proteome analysis identifies a novel interplay among commensal bacteria, metabolites and candidate targets in non-small cell lung cancer.

BACKGROUND: Accumulation of evidence suggests that the gut microbiome, its specific metabolites, and differentially expressed proteins (DEPs) are related to non-small cell lung cancer (NSCLC) pathogenesis. We now report the influences of the gut microbiota, metabolites, and DEPs on the mediation of NSCLC's chronic inflammation and immune dysregulation. METHODS: We conducted 16S ribosomal RNA sequencing for the gut microbiome in healthy volunteers and NSCLC patients. Liquid chromatography-mass spectrometry (LC-MS) analysis was employed to explore differences between metabolites and DEPs in serum samples. Additionally, LC-MS-based metabolomic analysis was conducted in 40 NSCLC tissues and 40 adjacent tissues. The omics data were separately analysed and integrated by using Spearman's correlation coefficient. Then, faecal microbiota transplantation (FMT) assay was used to assess the effects of the gut microbiome and specific metabolites in mice. RESULTS: Faecal microbiome analysis revealed gut microflora dysbiosis in NSCLC patients with Prevotella, Gemmiger, and Roseburia significantly upregulated at the genus level. Then, we identified that nervonic acid/all-trans-retinoic acid level was negatively related to Prevotella. Additionally, a total of core 8 DEPs were selected in the proteome analysis, which mainly participated in the production of IL-8 and NF-κB pathways. CRP, LBP, and CD14 were identified as potential biomarkers for NSCLC. Transplantation of faecal microbiota from patients with NSCLC or Prevotella copri-colonized recipient in mice resulted in inflammation and immune dysregulation. In turn, nervonic acid/all-trans-retinoic acid treatment improved the phenotype of C57BL/6 mice bearing P. copri-treated Lewis lung cancer (LLC). CONCLUSIONS: Overall, these results pointed out that P. copri-nervonic acid/all-trans-retinoic acid axis may contribute to the pathogenesis of NSCLC.

Comparative transcriptomic analysis reveals the regulatory mechanisms of catechins synthesis in different cultivars of Camellia sinensis.

Camellia sinensis (L.) O. Kuntze is used to produce tea, a beverage consumed worldwide. Catechins are major medically active components of C. sinensis and can be used clinically to treat hyperglycaemia, hypertension, and cancer. In this study, we aimed to identify the genes involved in catechins biosynthesis. To this end, we analysed transcriptome data from two different cultivars of C. sinensis using DNBSEQ technology. In total,47,717 unigenes were obtained from two cultivars of C. sinensis, of which 9429 were predicted as new unigenes. In our analyses of the Kyoto Encyclopedia of Genes and Genomes database, 212 unigenes encoding 13 key enzymes involved in catechins biosynthesis were identified; the structures of leucoanthocyanidin reductase and anthocyanidin reductase were spatially modelled. Some of these key enzymes were verified by real-time quantitative polymerase chain reaction, and multiple genes encoding plant resistance proteins or transcription factors were identified and analysed. Furthermore, two microRNAs involved in the regulation of catechins biosynthesis were explored. Differentially expressed genes involved in the flavonoid biosynthesis pathway were identified from pairwise comparisons of genes from different cultivars of tea plants. Overall, our findings expanded the number of publicly available transcript datasets for this valuable plant species and identified candidate genes related to the biosynthesis of C. sinensis catechins, thereby establishing a foundation for further in-depth studies of catechins biosynthesis in varieties or cultivars of C. sinensis.

A comparative study of three chemometrics methods combined with excitation-emission matrix fluorescence for quantification of the bioactive compounds aesculin and aesculetin in Cortex Fraxini.

Cortex Fraxini is an important traditional Chinese herbal medicine with various medical functions. Aesculin and aesculetin are the main effective components of Cortex Fraxini. The fluorescence signals of the two compounds have a high degree of overlap with each other, making quantitative analysis difficult with conventional analytical methods. In the present study, different chemometrics methods, including lasso regression (LAR), interval partial least squares (iPLS), and multidimensional partial least squares (N-PLS) methods, were employed and combined with excitation-emission matrix (EEM) fluorescence for the purpose of accurate quantification of aesculin and aesculetin in Cortex Fraxini samples. The most satisfactory results were obtained by using the N-PLS method based on the EEM spectra without scatterings, with correlation coefficient of calibration and prediction values higher than 0.9972 and 0.9962, respectively, root mean squared errors for calibration and prediction values lower than 0.0304 and 0.1165, respectively, and recovery values in the range of 83.32%-104.62%. The obtained credible models indicated that the N-PLS method combined with EEM spectra has the advantages of being green, low cost, and accurate and it is a good strategy for the determination of active compounds in complex samples. To further confirm the accuracy of the obtained results, the same samples were analyzed by the recognized ultra-performance liquid chromatography method.