Antenna-Biased Odorant Receptor PstrOR17 Mediates Attraction of Phyllotreta striolata to (S)-Cis-Verbenol and (-)-Verbenone.

Phyllotreta striolata, the striped flea beetle, is one of the most destructive pests in Brassicaceae plants worldwide. Given the drawbacks associated with long-term use of chemical insecticides, green strategies based on chemical ecology are an effective alternative for beetle control. However, the lack of information on beetle ecology has hindered the development of effective biocontrol strategies. In this report, we identified two odorants, (S)-cis-verbenol and (-)-verbenone, which displayed significant attraction for P. striolata (p < 0.05), indicating their great potential for P. striolata management. Using the Drosophila "empty neuron" system, an antenna-biased odorant receptor, PstrOR17, was identified as responsible for the detection of (-)-verbenone and (S)-cis-verbenol. Furthermore, the interactions between PstrOR17 and (-)-verbenone or (S)-cis-verbenol were predicted via modeling and molecular docking. Finally, we used RNAi to confirm that PstrOR17 is essential for the detection of (-)-verbenone and (S)-cis-verbenol to elicit an attraction effect. Our results not only lay a foundation for the development of new and effective nonchemical insecticide strategies based on (S)-cis-verbenol and (-)-verbenone, but also provide new insight into the molecular basis of odorant recognition in P. striolata.

Food-related inhibitory control deficits in young male adults with obesity: Behavioral and ERP evidence from a food-related go/no-go task.

PURPOSE: Obesity poses a pervasive challenge to global public health, which is linked to adverse physical health outcomes and cognitive decline. Cognitive function, particularly food-related cognitive function, plays a critical role in sustaining a healthy weight and mitigating the progression of obesity. The aim of this study was to investigate the behavioral and neuroelectronic aspects of food-related inhibitory functions in young adult males with obesity. METHODS: Forty-nine participants with obesity and healthy-weight were recruited (BMI = 35.83 ± 5.06 kg/m2 vs. 22.55 ± 1.73 kg/m2, age = 24.23 ± 4.55 years vs. 26.00 ± 3.97 years). A food-related Go/No-go task which included 6 distinct blocks in a randomized order was conducted to investigate the general and food-related inhibitory control. 180 stimulus images from the Food Picture Database encompassing high-calorie food, low-calorie food, and neutral images were selected. Behavioral (Go RT, Go ACC, No-go ACC) and event-related potential measures (N2 and P3 amplitude) during the food-related Go/No-go task were measured. RESULTS: The main findings indicated that the group with obesity exhibited lower No-go accuracy, slower go reaction times, and smaller P3 amplitudes in high-calorie, low-calorie foods, and neutral picture, compared to the normal-weight group, but with no group difference in N2. Additionally, high-calorie food induced larger N2 and P3 amplitude than the neutral stimuli. CONCLUSIONS: Young male adults with obesity exhibit poorer inhibitory control in both food and non-food domains, specifically in slower reaction time and reduced accuracy, featuring difficulties in neural resource recruitment during the inhibitory control process. Additionally, the P3 component could serve as sensitive indicators to reveal the neural mechanisms of inhibitory control deficits in obesity, while the N2 and P3 components may differentiate the neural differences between high-calorie foods and non-foods in inhibitory control processing. Food, especially high-calorie food, induces more neural resources and may exacerbate the poor inhibitory ability towards food in obesity. Targeted interventions such as exercise interventions, cognitive training as well as neuromodulation interventions are warranted in the future to improve impaired general and food-related inhibitory functions in the obese populations, offering both theoretical and practical frameworks for obesity prevention and treatment.

A potential link between aromatics-induced oviposition repellency behaviors and specific odorant receptor of Aedes albopictus.

BACKGROUND: The Asian tiger mosquito, Aedes albopictus, is a competent vector for the spread of several viral arboviruses including dengue, chikungunya, and Zika. Several vital mosquito behaviors linked to survival and reproduction are primarily dependent on a sophisticated olfactory system for semiochemical perception. However, a limited number of studies has hampered our understanding of the relationship between the A. albopictus acute olfactory system and the complex chemical world. RESULTS: Here, we performed a qRT-PCR assay on antennae from A. albopictus of differing sex, age and physiological states, and found that AalbOr10 was enriched in blood-fed female mosquitoes. We then undertook single sensillum recording to de-orphan AalbOr10 using a panel of physiologically and behaviorally relevant odorants in a Drosophila 'empty neuron' system. The results indicated that AalbOr10 was activated by seven aromatic compounds, all of which hampered egg-laying in blood-fed mosquitoes. Furthermore, using a post-RNA interference oviposition assay, we found that reducing the transcript level of AalbOr10 affected repellent activity mediated by 2-ethylphenol at low concentrations (10-4 vol/vol). Computational modeling and molecular docking studies suggested that hydrogen bonds to Y68 and Y150 mediated the interaction of 2-ethylphenol with AalbOr10. CONCLUSION: We reveal a potential link between aromatics-induced oviposition repellency behaviors and a specific odorant receptor in A. albopictus. Our findings provide a foundation for identifying active semiochemicals for the monitoring or controlling of mosquito populations. © 2024 Society of Chemical Industry.

Nuclear translocation of metabolic enzyme PKM2 participates in high glucose-promoted HCC metastasis by strengthening immunosuppressive environment.

Although some cohort studies have indicated a close association between diabetes and HCC, the underlying mechanism about the contribution of diabetes to HCC progression remains largely unknown. In the study, we applied a novel HCC model in SD rat with diabetes and a series of high glucose-stimulated cell experiments to explore the effect of a high glucose environment on HCC metastasis and its relevant mechanism. Our results uncovered a novel regulatory mechanism by which nuclear translocation of metabolic enzyme PKM2 mediated high glucose-promoted HCC metastasis. Specifically, high glucose-increased PKM2 nuclear translocation downregulates chemerin expression through the redox protein TRX1, and then strengthens immunosuppressive environment to promote HCC metastasis. To the best of our knowledge, this is the first report to elucidate the great contribution of a high glucose environment to HCC metastasis from a new perspective of enhancing the immunosuppressive microenvironment. Simultaneously, this work also highlights a previously unidentified non-metabolic role of PKM2 and opens a novel avenue for cross research and intervention for individuals with HCC and comorbid diabetes.

Empagliflozin attenuates liver fibrosis in high-fat diet/streptozotocin-induced mice by modulating gut microbiota.

The effects of SGLT2 inhibitors on hepatic fibrosis in diabetes remain unclear. This study aimed to investigate the effects of empagliflozin on liver fibrosis in high-fat diet/streptozotocin-induced mice and the correlation with gut microbiota. After the application of empagliflozin for 6 weeks, we performed oral glucose tolerance and intraperitoneal insulin tolerance tests to assess glucose tolerance and insulin resistance, and stained liver sections to evaluate histochemical and hepatic pathological markers of liver fibrosis. Moreover, 16S rRNA amplicon sequencing was performed on stool samples to explore changes in the composition of intestinal bacteria. We finally analysed the correlation between gut microbiome and liver fibrosis scores or indicators of glucose metabolism. The results showed that empagliflozin intervention improved glucose metabolism and liver function with reduced liver fibrosis, which might be related to changes in intestinal microbiota. In addition, the abundance of intestinal probiotic Lactobacillus increased, while Ruminococcus and Adlercreutzia decreased after empagliflozin treatment, and correlation analysis showed that the changes in microbiota were positively correlated with liver fibrosis and glucose metabolism. Overall, considering the contribution of the gut microbiota in metabolism, empagliflozin might have improved the beneficial balance of intestinal bacteria composition. The present study provides evidence and indicates the involvement of the gut-liver axis by SGLT2 inhibitors in T2DM with liver fibrosis.

Immunogenicity and protective efficacy of a trimeric full-length S protein subunit vaccine for porcine epidemic diarrhea virus.

Porcine epidemic diarrhea virus (PEDV) has caused serious economic losses to the pig husbandry worldwide, and the effects of existing commercialized vaccines are suboptimal. Therefore, research to develop an efficacious vaccine for prevention and control of PEDV is essential. In this study, we designed and produced trimerized proteins of full-length PEDV spike (S) protein, S1 subunit, and a tandem of multiple epitopes of S protein using an efficient mammalian expression vector system in HEK 293F cells. The immunogenicity of two commercial adjuvants, M401 and M103, was also evaluated in mice. Enzyme-linked immunosorbent assays demonstrated that all immunized mice generated highly systemic PEDV S-specific IgG and IgA antibodies. Mice in S/M103-immunized group generated the highest neutralizing antibody titer with 1:96. Compared with control group, the subunit vaccines elicited multifunctional CD3+CD4+ and CD3+CD8+ T cells, B220+CD19+ B cells, and CD3-CD49b+ natural killer cells in the spleen. PEDV S/M103 vaccine, which had the best immune effect, was selected for further evaluation in piglets. Immunization with S/M103 vaccine induced high levels of S-specific IgG, IgA, and neutralizing antibodies, and increased the proliferation of peripheral blood mononuclear cells and the expression levels of interferon-γ and interleukin-4 in peripheral blood of piglets. Virus challenge test results showed significantly lower diarrheal index scores and fecal viral loads, and less pathological damage to the intestines in S/M103-immunized piglets than in controls, indicating that S/M103 provides good protection against the virulent virus challenge. Our findings suggest that trimeric PEDV S/M103 has potential as a clinical vaccine candidate.

A synergistic regulation works in matrix stiffness-driven invadopodia formation in HCC.

Growing evidence has suggested that increased matrix stiffness can significantly strengthen the malignant characteristics of hepatocellular carcinoma (HCC) cells. However, whether and how increased matrix stiffness regulates the formation of invadopodia in HCC cells remain largely unknown. In the study, we developed different experimental systems in vitro and in vivo to explore the effects of matrix stiffness on the formation of invadopodia and its relevant molecular mechanism. Our results demonstrated that increased matrix stiffness remarkably augmented the migration and invasion abilities of HCC cells, upregulated the expressions of invadopodia-associated genes and enhanced the number of invadopodia. Two regulatory pathways contribute to matrix stiffness-driven invadopodia formation together in HCC cells, including direct triggering invadopodia formation through activating integrin ß1 or Piezo1/ FAK/Src/Arg/cortactin pathway, and indirect stimulating invadopodia formation through improving EGF production to activate EGFR/Src/Arg/cortactin pathway. Src was identified as the common hub molecule of two synergistic regulatory pathways. Simultaneously, activation of integrin ß1/RhoA/ROCK1/MLC2 and Piezo1/Ca2+/MLCK/MLC2 pathways mediate matrix stiffness-reinforced cell migration. This study uncovers a new mechanism by which mechanosensory pathway and biochemical signal pathway synergistically regulate the formation of invadopodia in HCC cells.

Analysis of differential membrane proteins related to matrix stiffness-mediated metformin resistance in hepatocellular carcinoma cells.

BACKGROUND: Our previous work shows that increased matrix stiffness not only alters malignant characteristics of hepatocellular carcinoma (HCC) cells, but also attenuates metformin efficacy in treating HCC cells. Here, we identified differential membrane proteins related to matrix stiffness-mediated metformin resistance for better understand therapeutic resistance of metformin in HCC. METHODS: Differential membrane proteins in HCC cells grown on different stiffness substrates before and after metformin intervention were screened and identified using isobaric tags for relative and absolute quantification (iTRAQ) labeling coupled with the liquid chromatography-tandem mass spectrometry (LC-MS/MS), then bioinformatic analysis were applied to determine candidate membrane protein and their possible signaling pathway. RESULTS: A total of 5159 proteins were identified and 354 differential membrane proteins and membrane associated proteins, which might be associated with matrix stiffness-mediated metformin resistance were discovered. Then 94 candidate membrane proteins including 21 up-regulated protein molecules and 73 down-regulated protein molecules were further obtained. Some of them such as Annexin A2 (ANXA2), Filamin-A (FLNA), Moesin (MSN), Myosin-9 (MYH9), Elongation factor 2 (eEF2), and Tax1 binding Protein 3 (TAX1BP3) were selected for further validation. Their expressions were all downregulated in HCC cells grown on different stiffness substrates after metformin intervention. More importantly, the degree of decrease was obviously weakened on the higher stiffness substrate compared with that on the lower stiffness substrate, indicating that these candidate membrane proteins might contribute to matrix stiffness-mediated metformin resistance in HCC. CONCLUSIONS: There was an obvious change in membrane proteins in matrix stiffness-mediated metformin resistance in HCC cells. Six candidate membrane proteins may reflect the response of HCC cells under high stiffness stimulation to metformin intervention, which deserve to be investigated in the future.

Leucine to tryptophane substitution in the pore helix IIP1 confer sodium channel resistance to pyrethroids and DDT.

Aedes aegypti is responsible for transmitting a variety of arboviral infectious diseases such as dengue and chikungunya. Insecticides, particularly pyrethroids, are used widely for mosquito control. However, intensive used of pyrethroids has led to the selection of kdr mutations on sodium channels. L982W, locating in the PyR1 (Pyrethroid receptor site 1), was first reported in Ae. aegypti populations collected from Vietnam. Recently, the high frequency of L982W was detected in pyrethroid-resistant populations of Vietnam and Cambodia, and also concomitant mutations L982W + F1534C was detected in both countries. However, the role of L982W in pyrethroid resistance remains unclear. In this study, we examined the effects of L982W on gating properties and pyrethroid sensitivity in Xenopus oocytes. We found that mutations L982W and L982W + F1534C shifted the voltage dependence of activation in the depolarizing direction, however, neither mutations altered the voltage dependence of inactivation. L982W significantly reduced channel sensitivity to Type I pyrethroids, permethrin and bifenthrin, and Type II pyrethroids, deltamethrin and cypermethrin. No enhancement was observed when synergized with F1534C. In addition, L982W and L982W + F1534C mutations reduced the channel sensitivity to DDT. Our results illustrate the molecular basis of resistance mediates by L982W mutation, which will be helpful to understand the interacions of pyrethroids or DDT with sodium channels and develop molecular markers for monitoring pest resistance to pyrethroids and DDT.

Correlation between the IgG/IgA Antibody Response against PEDV Structural Protein and Virus Neutralization.

Porcine epidemic diarrhea (PED) is a highly contagious intestinal infectious disease caused by porcine epidemic diarrhea virus (PEDV). Large-scale outbreaks of PEDV have caused huge economic losses to the pig industry since 2010. Neutralizing antibodies play a pivotal role in protecting piglets from enteric infections. However, there has been no systematic report on the correlations between neutralizing antibody titers (NTs) and absorbance values of IgG or IgA to all PEDV individual structural proteins in clinical serum, fecal, and colostrum samples. In this study, the spike protein S1 domain (S1), membrane protein (M), envelope protein (E), and nucleocapsid protein (N) of the variant PEDV strain AH2012/12 were expressed and purified by using the human embryonic kidney (HEK) 293F expression system. A total of 92 clinical serum samples, 46 fecal samples, and 33 colostrum samples were collected, and the correlations between IgG or IgA absorbance values and NTs were analyzed. R2 values revealed that anti-S1 IgA absorbance values show the highest agreement with NTs in all serum, fecal, and colostrum samples, followed by the N protein. The correlations between anti-E or M IgA and NTs were very low. However, in the colostrum samples, both IgG and IgA to S1 showed high correlations with NTs. In addition, compared with E and M, the highest correlations of IgA absorbance values were with N and S1 in serum and fecal samples. Overall, this study revealed the highest correlation between NTs and IgA to PEDV S1 protein. Therefore, the diagnostic method with anti-S1 IgA can be used as a powerful tool for assessing the immune status of pigs. IMPORTANCE The humoral immune response plays an important role in virus neutralization. Against PEDV, both IgG and the mucosal immune component IgA play roles in virus neutralization. However, which plays a more prominent role and whether there are differences in different tissue samples are not clearly reported. Additionally, the relationship between IgG and IgA against individual structural proteins and viral neutralization remains unclear. In this study, we systematically determined the relationship between IgG and IgA against all PEDV structural proteins and viral neutralization in different clinical samples and found the highest correlation between neutralization activity and IgA to PEDV S1 protein. Our data have important guiding implications in the evaluation of immune protection.

Transcriptomic and antiviral analyses of PoIFN-Delta5 against porcine enteric viruses in porcine intestinal epithelial cells.

The interferon-delta family was first reported in domestic pigs and belongs to the type I interferon (IFN-I) family. The enteric viruses could cause diarrhea in newborn piglets with high morbidity and mortality. We researched the function of the porcine IFN-delta (PoIFN-δ) family in the porcine intestinal epithelial cells (IPEC-J2) cells infected with porcine epidemic diarrhea virus (PEDV). Our study found that all PoIFN-δs shared a typical IFN-I signature and could be divided into five branches in the phylogenic tree. Different strains of PEDV could induce typical IFN transitorily, and the virulent strain AH2012/12 had the strongest induction of porcine IFN-δ and IFN-alpha (PoIFN-α) in the early stage of infection. In addition, it was found that PoIFN-δ5/6/9/11 and PoIFN-δ1/2 were highly expressed in the intestine. PoIFN-δ5 had a better antiviral effect on PEDV compared to PoIFN-δ1 due to its higher induction of ISGs. PoIFN-δ1 and PoIFN-δ5 also activated JAK-STAT and IRS signaling. For other enteric viruses, transmissible gastroenteritis virus (TGEV), porcine deltacoronavirus (PDCoV), and porcine rotavirus (PoRV), PoIFN-δ1 and PoIFN-δ5 both showed an excellent antiviral effect. Transcriptome analyses uncovered the differences in host responses to PoIFN-α and PoIFN-δ5 and revealed thousands of differentially expressed genes were mainly enriched in the inflammatory response, antigen processing and presentation, and other immune-related pathways. PoIFN-δ5 would be a potential antiviral drug, especially against porcine enteric viruses. These studies were the first to report the antiviral function against porcine enteric viruses and broaden the new acquaintances of this type of interferon though not novelly discovered.

Zwitterionic surfactant as an additive for efficient electrophoretic separation of easily absorbed rhodamine dyes on plastic microchips.

Plastic microchips possess the advantages of easy fabrication and low-cost, but their surface properties are frequently incompatible with electrophoretic separation without proper surface modification. Meanwhile, the separation microchannels on typical microchips are usually only a few centimeters long, the pressurized flow may significantly affect the electrophoretic separation if their inner diameters (id) are relatively larger (approximately > 50 µm), viscous separation medium is therefore required for efficient separation. Herein, a zwitterionic surfactant, N-hexadecyl-N,N-dimethyl-3-ammonio-1-propane sulfonate (HDAPS), was used as a multifunctional additive to inhibit the analyte adsorption, improve the surface status, control Joule heating and modulate the resolution on cyclic olefin copolymer microchips with 80 µm id, 5 cm long separation microchannels, eliminating the necessity of viscous polymeric additives. The effectiveness of HDAPS was compared with an ionic polymeric additive, poly(diallydimethylammonium chloride). The streaming potential and electroosmotic flow measurements indicated an effective inhibition of the adsorption of rhodamine B and a stable negative surface charge with zwitterionic HDAPS. Using 15 mmol/L HDAPS, 40% (v/v) methanol, and 10 mmol/L boric acid (pH 3.2) as the running buffer, rapid separation of four rhodamines was achieved within 90 s under a separation electric field of 520 V/cm. The theoretical plate numbers were in a range of 5.0×105-6.9×105/m. The relative standard deviations were no more than 0.9% for retention time and 1.5% for peak area. The proposed system was verified by the determination of rhodamines in eyeshadow and wolfberry, with standard recoveries in a range of 98.2%-101.4%.

Fibrinogen-to-Neutrophil Ratio as a New Predictor of Central Lymph Node Metastasis in Patients with Papillary Thyroid Cancer and Type 2 Diabetes Mellitus.

Background: Many patients have a higher risk of thyroid cancer if they have both papillary thyroid carcinoma (PTC) and Type 2 diabetes mellitus (T2DM). Meanwhile, the primary reason for local PTC recurrence is cervical lymph node metastasis. Therefore, the prognosis of patients affects how cervical lymph nodes are managed during surgery. Due to surgical complications such as laryngeal nerve palsy and hypocalcemia, it is still debatable whether to prevent central lymph node dissection (CLND). Predicting central lymph node metastasis (CLNM) is crucial to direct CLND. It is unclear how important the fibrinogen-to-neutrophil ratio (FNR) is in thyroid cancer, so we looked into how it might help patients with PTC and T2DM predict CLNM. Patients and methods: Wenzhou Medical University's First Affiliated Hospital provided us with 413 patients with PTC and T2DM, randomly divided into a training set (N = 292) and a validation set (N = 121). Univariate and multivariate logistic regression analyses were used to identify independent risk factors. After constructing a nomogram, the validity of the model was evaluated. Results: The maximum tumor diameter, high-density lipoprotein, thyroxine, triglyceride, lymphocyte, and FNR were all identified as independent risk factors by multivariate logistic regression analysis. The C index of the training set was 0.775, and the validation set was 0.654. Conclusion: In patients with PTC and T2DM, preoperative FNR was an independent risk factor for CLNM.

Silencing of dre4 Contributes to Mortality of Phyllotreta striolata.

The striped flea beetle, Phyllotreta striolata, is one of the most destructive pests of Cruciferae crops worldwide. RNA interference (RNAi) is a promising alternative strategy for pest biological control, which overcomes the weakness of synthetic insecticides, such as pest resistance, food safety problems and toxicity to non-target insects. The homolog of Spt16/FACT, dre4 plays a critical role in the process of gene transcription, DNA repair, and DNA replication; however, the effects of dre4 silencing in P. striolata remain elusive. In this study, we cloned and characterized the full-length dre4 from P. striolata and silenced Psdre4 through microinjection and oral delivery; it was found that the silencing of dre4 contributed to the high mortality of P. striolata in both bioassays. Moreover, 1166 differentially regulated genes were identified after Psdre4 interference by RNA-seq analysis, which might have been responsible for the lethality. The GO analysis indicated that the differentially regulated genes were classified into three GO functional categories, including biological process, cellular component, and molecular function. The KEGG analysis revealed that these differentially regulated genes are related to apoptosis, autophagy, steroid hormone biosynthesis, cytochrome P450 and other signaling pathways. Our results suggest that Psdre4 is a fatal RNAi target and has significant potential for the development of RNA pesticides for P. striolata management.

Dental Lesion Segmentation Using an Improved ICNet Network with Attention.

Precise segmentation of tooth lesions is critical to creation of an intelligent tooth lesion detection system. As a solution to the problem that tooth lesions are similar to normal tooth tissues and difficult to segment, an improved segmentation method of the image cascade network (ICNet) network is proposed to segment various lesion types, such as calculus, gingivitis, and tartar. First, the ICNet network model is used to achieve real-time segmentation of lesions. Second, the Convolutional Block Attention Module (CBAM) is integrated into the ICNet network structure, and large-size convolutions in the spatial attention module are replaced with layered dilated convolutions to enhance the relevant features while suppressing useless features and solve the problem of inaccurate lesion segmentations. Finally, part of the convolution in the network model is replaced with an asymmetric convolution to reduce the calculations added by the attention module. Experimental results show that compared with Fully Convolutional Networks (FCN), U-Net, SegNet, and other segmentation algorithms, our method has a significant improvement in the segmentation effect, and the image processing frequency is higher, which satisfies the real-time requirements of tooth lesion segmentation accuracy.

Activation of Piezo1 contributes to matrix stiffness-induced angiogenesis in hepatocellular carcinoma.

BACKGROUND: Despite integrin being highlighted as a stiffness-sensor molecule in matrix stiffness-driven angiogenesis, other stiffness-sensor molecules and their mechanosensory pathways related to angiogenesis in hepatocellular carcinoma (HCC) remain obscure. Here, we explored the interplay between Piezo1 and integrin ß1 in the mechanosensory pathway and their effects on HCC angiogenesis to better understand matrix stiffness-induced angiogenesis. METHODS: The role of Piezo1 in matrix stiffness-induced angiogenesis was investigated using orthotopic liver cancer SD rat models with high liver stiffness background, and its clinical significance was evaluated in human HCC tissues. Matrix stiffness-mediated Piezo1 upregulation and activation were assayed using an in vitro fibronectin (FN)-coated cell culture system with different stiffness, Western blotting and Ca2+ probe. The effects of shPiezo1-conditioned medium (CM) on angiogenesis were examined by tube formation assay, wound healing assay and angiogenesis array. The underlying mechanism by which Piezo1 participated in matrix stiffness-induced angiogenesis was analyzed by microRNA quantitative real-time polymerase chain reaction (qRT-PCR), matrix stiffness measurement, dual-luciferase reporter assay, ubiquitination assay and co-immunoprecipitation. RESULTS: Increased matrix stiffness significantly upregulated Piezo1 expression at both cellular and tissue levels, and high expression of Piezo1 indicated an unfavorable prognosis. High matrix stiffness also noticeably enhanced the activation level of Piezo1, similar to its expression level. Piezo1 knockdown significantly suppressed tumor growth, angiogenesis, and lung metastasis of HCC rat models with high liver stiffness background. shPiezo1-CM from HCC cells attenuated tube formation and migration abilities of vascular endothelial cells remarkably, and analysis of differentially expressed pro-angiogenic factors revealed that Piezo1 promoted the expression and secretion of vascular endothelial growth factor (VEGF), CXC chemokine ligand 16 (CXCL16) and insulin-like growth factor binding protein 2 (IGFBP2). Matrix stiffness-caused Piezo1 upregulation/activation restrained hypoxia inducible factor-1α (HIF-1α) ubiquitination, subsequently enhanced the expression of downstream pro-angiogenic factors to accelerate HCC angiogenesis. Besides, collagen 1 (COL1)-reinforced tissue stiffening resulted in more expression of Piezo1 via miR-625-5p. CONCLUSIONS: This study unravels a new mechanism by which the integrin ß1/Piezo1 activation/Ca2+ influx/HIF-1α ubiquitination/VEGF, CXCL16 and IGFBP2 pathway participates in matrix stiffness-driven HCC angiogenesis. Simultaneously, a positive feedback regulation loop as stiff matrix/integrin ß1/miR-625-5p/Piezo1 and COL1/stiffer matrix mediates matrix stiffness-caused Piezo1 upregulation.

Changes in working memory performance and cortical activity during acute aerobic exercise in young adults.

This study aimed to examine the concurrent performance of working memory and cortical activity during acute aerobic exercise in young adults. In a crossover study design, 27 young adults (mean age = 22.7 ± 3.4 years, 15 women) participated in two experimental conditions in a randomized order: (1) sitting condition (without exercise) and (2) cycling condition (moderate-intensity exercise). Working memory was measured with a modified version of the n-back task. A functional near-infrared spectroscopy (fNIRS) was used to measure cortex activation. In the cycling condition, response time (RT) for the n-back task was significantly faster (p < 0.05). No differences in accuracy were observed between the sitting and cycling conditions. The fNIRS results showed that the oxygenated hemoglobin (oxy-Hb) concentrations in the bilateral frontopolar area (p < 0.05), dorsolateral prefrontal cortex (p < 0.05), and right premotor and supplementary cortex (p < 0.05) were decreased while cycling. The findings indicated that the concurrent performance of working memory was improved during acute aerobic exercise, whereas cortical activity was decreased in some brain regions.

High Temperature Tensile Fracture Behavior of Copper-Containing Austenitic Antibacterial Stainless Steel.

The mechanical properties and deformation microstructure of cast 304 Cu-containing austenitic stainless steel at 10-3/s strain rate in the range of 700~1200 °C were studied by Gleeble thermal simulator, metallographic microscope and scanning electron microscope. The results showed that the thermoplasticity of 304 Cu-containing austenitic stainless steel was higher than 60% when the temperature was higher than 1000 °C, and the tensile strength as a whole decreased with the increase in temperature. During the tensile process, the morphology and content of ferrite in the test steel were the main factors affecting the high-temperature thermoplastic of the billet. The inclusions near the fracture and the existence of ferrite at the grain boundary greatly affected the formation of microcracks and holes and the fracture.

Molecular and functional characterization of a conserved odorant receptor from Aedes albopictus.

BACKGROUND: The Asian tiger mosquito Aedes albopictus is a competent vector of several viral arboviruses including yellow fever, dengue fever, and chikungunya. Several vital mosquito behaviors (e.g., feeding, host-seeking, mating, and oviposition) are primarily dependent on the olfactory system for semiochemicals detection and discrimination. However, the limited number of studies hampers our understanding of the relationships between the Ae. albopictus olfactory system and the complex chemical world. METHODS: We performed RT-qPCR assay on antennae of Ae. albopictus mosquitoes of different sexes, ages and physiological states, and found odorant receptor 11 (AalbOr11) enriched in non-blood-fed female mosquitoes. Then, we examined the odorant preference with a panel of physiologically and behaviorally relevant odorants in Xenopus oocytes. RESULTS: The results indicated that AalbOr11 could be activated by ten aromatics, seven terpenes, six heterocyclics, and three alcohols. Furthermore, using post-RNA interference (RNAi) hand-in-cage assay, we found that reducing the transcript level of AalbOr11 affected the repellency activity mediated by (+)-fenchone at a lower concentration (0.01% v/v). CONCLUSIONS: Using in vitro functional characterization, we found that AalbOr11 was a broadly tuned receptor. Moreover, we found that AalbOr11 shared a conserved odorant reception profile with homologous Anopheles gambiae Or11. In addition, RNAi and bioassay suggested that AablOr11 might be one of the receptors mediating (+)-fenchone repellency activity. Our study attempted to link odor-induced behaviors to odorant reception and may lay the foundation for identifying active semiochemicals for monitoring or controlling mosquito populations.