Optimization of cancer immunotherapy through pyroptosis: A pyroptosis-related signature predicts survival benefit and potential synergy for immunotherapy in glioma.

Background: Pyroptosis is a critical type of programmed cell death that is strongly associated with the regulation of tumor and immune cell functions. However, the role of pyroptosis in tumor progression and remodeling of the tumor microenvironment in gliomas has not been extensively studied. Thus, in this study, we aimed to establish a comprehensive pyroptosis-related signature and uncover its potential clinical application in gliomas. Methods: The TCGA glioma cohort was obtained and divided into training and internal validation cohorts, while the CGGA glioma cohort was used as an external validation cohort. Unsupervised consensus clustering was performed to identify pyroptosis-related expression patterns. A Cox regression analysis was performed to establish a pyroptosis-related risk signature. Real-time quantitative PCR was performed to analyze the expression of signature genes in glioma tissues. Immune infiltration was analyzed and validated by immunohistochemical staining. The expression patterns of signature genes in different cell types were analyzed using single-cell RNA sequencing data. Finally, therapeutic responses to chemotherapy, immunotherapy, and potential small-molecule inhibitors were investigated. Results: Patients with glioma were stratified into clusters 1 and 2 based on the expression patterns of pyroptosis-related genes. Cluster 2 showed a longer overall (P<0.001) and progression-free survival time (P<0.001) than Cluster 1. CD8+ T cell enrichment was observed in Cluster 1. A pyroptosis-related risk signature (PRRS) was then established. The high PRRS group showed a significantly poorer prognosis than the low PRRS group in the training cohort (P<0.001), with validation in the internal and external validation cohorts. Immunohistochemical staining demonstrated that CD8+ T cells were enriched in high PRRS glioma tissues. PRRS genes also showed cell-specific expression in tumor and immune cells. Moreover, the high PRRS risk group showed higher temozolomide sensitivity and increased response to anti-PD1 treatment in a glioblastoma immunotherapy cohort. Finally, Bcl-2 inhibitors were screened as candidates for adjunct immunotherapy of gliomas. Conclusion: The pyroptosis-related signature established in this study can be used to reliably predict clinical outcomes and immunotherapy responses in glioma patients. The correlation between the pyroptosis signature and the tumor immune microenvironment may be used to further guide the sensitization of glioma patients to immunotherapy.

Lighting a Fire: Gasdermin-Mediated Pyroptosis Remodels the Glioma Microenvironment and Promotes Immune Checkpoint Blockade Response.

Pyroptosis is a proinflammatory programmed cell death pathway mediated by gasdermins. Exploring the role of pyroptosis can provide new insights into tumor malignancy. The most recent studies on pyroptosis have focused on tumor cells. However, the effects of pyroptosis on the tumor microenvironment (TME), immunotherapeutic responses, and efficacy have been neglected, especially in case of glioma. In this study, four independent glioma cohorts comprising 1,339 samples and a pan-cancer cohort comprising 10,535 tumor samples were analyzed. The relationships among pyroptosis status, prognosis, microenvironment cellular components, and clinical and biological phenotypes were investigated through the identification of pyroptosis subtypes, construction of a gasdermin-related prognostic index (GPI), and evaluation of immunological characteristics in glioma. The Genomics of Drug Sensitivity in Cancer database and "pRRophetic" package in R were used to estimate temozolomide (TMZ) sensitivity. The "Submap" package and external immunotherapy cohorts were used to investigate and confirm the role of GPI in response to and efficacy of immunotherapy in glioma. Finally, potential small-molecule compounds related to GPI were identified using the connectivity map database and mode-of-action analysis. We identified three different pyroptosis subtypes: cluster 1 (C1) characterized by a higher GPI, while cluster 2 (C2) and cluster 3 (C3) characterized by a lower GPI. The high GPI of C1 was associated with glioma progression and worse prognoses, whereas the low GPI of subtype C2 and C3 was associated with better prognoses. However, patients with high GPIs were found to be more sensitive to TMZ and immune checkpoint blockade than those with low GPIs. Furthermore, gasdermin D may be a principal potential biomarker and play key roles in pyroptosis-inducible therapy combined with immunotherapy in glioma. This study provides a clinical, biological, and molecular landscape of pyroptosis and suggests that pyroptosis of glioma cells may perform the dual function of promoting both tumorigenesis and antitumor immunity.

A near-ambient pressure flow reactor coupled with polarization-modulation infrared reflection absorption spectroscopy for operando studies of heterogeneous catalytic reactions over model catalysts.

The model catalyst approach is often used for fundamental investigations of complex heterogeneous catalysis, in which operando characterizations are critical. A flow reactor is usually adopted for gas-solid heterogeneous catalytic reactions. Herein, we report a home-designed near-ambient pressure (NAP) flow reactor coupled with polarization-modulation infrared reflection absorption spectroscopy (PM-IRAS) and an online quadrupole mass spectrometer for operando studies of heterogeneous catalytic reactions over model catalysts. A unique gas supply system is designed and manufactured to enable a stable gas inlet to the NAP flow reactor at pressures up to ∼100 mbar. An ultrahigh vacuum chamber equipped with the facilities for x-ray photoelectron spectroscopy, low-energy electron diffraction, thermal desorption spectroscopy, E-beam evaporation source, and ion sputtering gun is connected to the NAP flow reactor via a gate valve for preparations and routine characterizations of model catalysts. The functions of the system are demonstrated by in situ PM-IRAS characterization of CO adsorption on Pt(111) and operando characterizations of CO oxidation on Pt(111) under NAP conditions.

In Situ Generated Ti3+-Mediated Photocatalytic Methanol Decomposition to Carbon Monoxide and Hydrogen on a Rutile TiO2(100) Surface.

Photocatalysis of methanol on the TiO2 surface is a prototype of photocatalytic reactions. Here, we unveil a synergistic effect of photoexcited electrons and holes on converting methanol to CO and H2 on a rutile TiO2(100) surface. Upon Hg light irradiation, photoexcited holes oxidize methoxy species at the 5-fold coordinated Ti4+ sites sequentially to formaldehyde and formate intermediates, while photoexcited electrons reduce the associated Ti4+ sites to Ti3+ sites. The formate intermediates selectively decompose to CO and H2 mediated by the Ti3+ sites at elevated temperatures. These results greatly enrich methanol photochemistry on the TiO2 surface and point to a surface structure engineering strategy of oxide photocatalysts for photocatalytic direct methanol decomposition to CO and H2.

Fine cubic Cu2O nanocrystals as highly selective catalyst for propylene epoxidation with molecular oxygen.

Propylene epoxidation with O2 to propylene oxide is a very valuable reaction but remains as a long-standing challenge due to unavailable efficient catalysts with high selectivity. Herein, we successfully explore 27 nm-sized cubic Cu2O nanocrystals enclosed with {100} faces and {110} edges as a highly selective catalyst for propylene epoxidation with O2, which acquires propylene oxide selectivity of more than 80% at 90-110 °C. Propylene epoxidation with weakly-adsorbed O2 species at the {110} edge sites exhibits a low barrier and is the dominant reaction occurring at low reaction temperatures, leading to the high propylene oxide selectivity. Such a weakly-adsorbed O2 species is not stable at high reaction temperatures, and the surface lattice oxygen species becomes the active oxygen species to participate in propylene epoxidation to propylene oxide and propylene partial oxidation to acrolein at the {110} edge sites and propylene combustion to CO2 at the {100} face sites, which all exhibit high barriers and result in decreased propylene oxide selectivity.

Oxidative Coupling of Methanol with Molecularly Adsorbed Oxygen on Au Surface to Methyl Formate.

Supported Au catalysts efficiently catalyze the oxidative coupling of methanol with O2 to methyl formate, in which the atomic O species (O(a)) formed via O2 dissociation on the Au surface has been considered as the active oxygen species. Herein we report for the first time that the oxidative coupling of methanol can occur facilely with molecularly adsorbed O2 species (O2(a)) on a Au(997) surface at temperatures as low as around 125 K, while that with O(a) occurs at around 175 K. Both experimental and theoretical calculation results demonstrate a novel reaction mechanism of oxidative coupling of CH3OH with O2(a) via a dioxymethylene (H2COO) intermediate, resulting in the production of both HCOOCH3 and HCOOCH3. These results reveal the unique reactivity of molecularly adsorbed O2 species on Au surfaces for low-temperature oxidation reactions.

A Ferroptosis-Related Gene Prognostic Index to Predict Temozolomide Sensitivity and Immune Checkpoint Inhibitor Response for Glioma.

Background: Gliomas are highly lethal brain tumors. Despite multimodality therapy with surgery, radiotherapy, chemotherapy, and immunotherapy, glioma prognosis remains poor. Ferroptosis is a crucial tumor suppressor mechanism that has been proven to be effective in anticancer therapy. However, the implications of ferroptosis on the clinical prognosis, chemotherapy, and immune checkpoint inhibitor (ICI) therapy for patients with glioma still need elucidation. Methods: Consensus clustering revealed two distinct ferroptosis-related subtypes based on the Cancer Genome Atlas (TCGA) glioma dataset (n = 663). Subsequently, the ferroptosis-related gene prognostic index (FRGPI) was constructed by weighted gene co-expression network analysis (WGCNA) and "stepAIC" algorithms and validated with the Chinese Glioma Genome Atlas (CGGA) dataset (n = 404). Subsequently, the correlation among clinical, molecular, and immune features and FRGPI was analyzed. Next, the temozolomide sensitivity and ICI response for glioma were predicted using the "pRRophetic" and "TIDE" algorithms, respectively. Finally, candidate small molecular drugs were defined using the connectivity map database based on FRGPI. Results: The FRGPI was established based on the HMOX1, TFRC, JUN, and SOCS1 genes. The distribution of FRGPI varied significantly among the different ferroptosis-related subtypes. Patients with high FRGPI had a worse overall prognosis than patients with low FRGPI, consistent with the results in the CGGA dataset. The final results showed that high FRGPI was characterized by more aggressive phenotypes, high PD-L1 expression, high tumor mutational burden score, and enhanced temozolomide sensitivity; low FRGPI was associated with less aggressive phenotypes, high microsatellite instability score, and stronger response to immune checkpoint blockade. In addition, the infiltration of memory resting CD4+ T cells, regulatory T cells, M1 macrophages, M2 macrophages, and neutrophils was positively correlated with FRGPI. In contrast, plasma B cells and naïve CD4+ T cells were negatively correlated. A total of 15 potential small molecule compounds (such as depactin, physostigmine, and phenacetin) were identified. Conclusion: FRGPI is a promising gene panel for predicting the prognosis, immune characteristics, temozolomide sensitivity, and ICI response in patients with glioma.

Safety, Tolerability, Pharmacokinetics, and Concentration-QTc Analysis of Tetrodotoxin: A Randomized, Dose Escalation Study in Healthy Adults.

Tetrodotoxin (TTX) is a highly specific voltage-gated sodium channel (VGSC) blocker in clinical evaluation as a peripheral-acting analgesic for chronic pain. This study presents the first published results of the safety including cardiac liability of TTX at therapeutic-relevant concentrations in twenty-five healthy adults. Randomized, double-blind, placebo-, and positive- (moxifloxacin) controlled study evaluated single ascending doses of 15 µg, 30 µg, and 45 µg TTX over 3 periods with a 7-day washout between each period. Subcutaneous injections of TTX were readily absorbed, reaching maximum plasma concentration (Cmax) within 1.5 h. Both extent of exposure (AUC) and Cmax increased in proportion to dose. No QT prolongation was identified by concentration-QTc analysis and the upper bounds of the two-sided 90% confidence interval of predicted maximum baseline and placebo corrected QTcF (ΔΔQTcF) value did not exceed 10 ms for all tetrodotoxin doses, thereby meeting the criteria of a negative QT study. Safety assessments showed no clinically relevant changes with values similar between all groups and no subject withdrawing due to adverse events. Paresthesia, oral-paresthesia, headache, dizziness, nausea, and myalgia were the most common TEAEs (overall occurrence ≥5%) in the TTX treatment groups. TTX doses investigated in this study are safe, well-tolerated, and lack proarrhythmic proclivity.

Surface chemistry and photochemistry of small molecules on rutile TiO2(001) and TiO2(011)-(2 × 1) surfaces: The crucial roles of defects.

Surface chemistry and photochemistry of small molecules on the rutile TiO2(001) and TiO2(011)-(2 × 1) surfaces were studied by low energy electron diffraction, thermal desorption spectroscopy, and x-ray photoelectron spectroscopy. It was found that the TiO2(001) surface mainly exhibits the defects of Ti interstitials in the near-surface region, while the TiO2(011)-(2 × 1) surface mainly exhibits the defects of double-oxygen vacancies. The defect structures of TiO2 surfaces strongly affect their adsorption and thermal/photodesorption behaviors. On the TiO2(001) surface, CH3OH and H2O dissociatively adsorb at the surface Ti sites near Ti interstitials; O2 molecularly adsorbs at the surface Ti sites adjacent to Ti interstitials, forming photoactive O2 species that undergoes a hole-mediated photodesorption process; CO adsorbs at the nearest surface Ti sites close to the Ti interstitials, but CO2 does not, and the resulting CO species is photoactive; and both CO and CO2 species adsorbed at the normal Ti4+ sites are photoinactive. On the TiO2(011)-(2 × 1) surface, O2 adsorbs only at the double-oxygen vacancy sites, and the resulting O2 species dissociates to form two oxygen atoms to refill in the oxygen vacancies upon heating; CO2 adsorbs at the double-oxygen vacancy sites, but CO does not, and the resulting CO2 species is photoactive; and both CO and CO2 species adsorbed at the surface Ti4+ sites are photoinactive. These results broaden the fundamental understandings of the chemistry and photochemistry of TiO2 surfaces, and the established structure-reactivity relation of small molecules on TiO2 surfaces is useful in probing complex structures of TiO2 powder catalysts.

Mechanical Behavior Investigation of 4H-SiC Single Crystal at the Micro-Nano Scale.

In this paper, theoretical models of the critical indentation depth and critical force on brittle materials using cleavage strength and contact theory are proposed. A Berkovich indenter is adopted for nanoindentation tests on a 4H-SiC single crystal sample to evaluate its mechanical behaviors. The stages of brittle material deformation (elastic, plastic, and brittle) can be characterized by the load versus indentation depth curves through the nanoindentation test. The curve of the elastic deformation stage follows the Hertz contact theory, and plastic deformation occurs at an indentation depth of up to 10 nm. The mechanism of 4H-SiC single crystal cracking is discussed, and the critical indentation depth and critical force for the plastic-brittle transition are obtained through the occurrence of the pop-in point. This shows that the theoretical results have good coherence with the test results. Both the values of the elastic modulus and hardness decrease as the crack length increases. In order to obtain more accurate mechanical property values in the nanoindentation test for brittle materials such as SiC, GaN, and sapphire, an appropriate load that avoids surface cracks should be adopted.

Modeling and Experiment of the Critical Depth of Cut at the Ductile-Brittle Transition for a 4H-SiC Single Crystal.

In this paper, a theoretical model of the critical depth of cut of nanoscratching on a 4H-SiC single crystal with a Berkovich indenter is proposed, and a series of scratch tests in a nanomechanical test system was performed. Through nanoindentation experimentation on fused quartz, the Berkovich indenter nose radius was indirectly confirmed using least squares. The range of critical depths of cut at the ductile-brittle transition was obtained by SEM observation, and the size of cracks was amplified with increasing scratching depth. The theoretical result of the critical depth of cut at the ductile-brittle transition for a 4H-SiC single crystal is 91.7 nm, which is close to the first obvious pop-in point of the relation curve between tangential force and lateral displacement. Repeated experimental results show good consistency and good agreement with other references.

Cytokinin-induced parthenocarpy of San Pedro type fig (Ficus carica L.) main crop: explained by phytohormone assay and transcriptomic network comparison.

KEY MESSAGE: CPPU-induced San Pedro type fig main crop parthenocarpy exhibited constantly increasing IAA content and more significantly enriched KEGG pathways in the receptacle than in female flowers. N-(2-chloro-4-pyridyl)-N-phenylurea (CPPU) was applied to San Pedro fig (Ficus carica L.) main crop to induce parthenocarpy; the optimal effect was obtained with 25 mg L-1 application to syconia when female flowers were at anthesis. To elucidate the key expression changes in parthenocarpy conversion, significant changes in phytohormone level and transcriptome of fig female flowers and receptacles were monitored. HPLC-MS revealed increased IAA content in female flowers and receptacle 2, 4 and 10 days after treatment (DAT), decreased zeatin level in the receptacle 2, 4 and 10 DAT, decreased GA3 content 2 and 4 DAT, and increased GA3 content 10 DAT. ABA level increased 2 and 4 DAT, and decreased 10 DAT. CPPU-treated syconia released more ethylene than the control except 2 DAT. RNA-Seq and bioinformatics analysis revealed notably more differentially expressed KEGG pathways in the receptacle than in female flowers. In the phytohormone gene network, GA-biosynthesis genes GA20ox and GA3ox were upregulated, along with GA signal-transduction genes GID1 and GID2, and IAA-signaling genes AUX/IAA and GH3. ABA-biosynthesis gene NCED and signaling genes PP2C and ABF were downregulated 10 DAT. One ACO gene showed consistent upregulation in both female flowers and receptacle after CPPU treatment, and more than a dozen of ERFs demonstrated opposing changes in expression. Our results revealed early-stage spatiotemporal phytohormone and transcriptomic responses in CPPU-induced San Pedro fig main crop parthenocarpy, which could be valuable for further understanding the nature of the parthenocarpy of different fig types.

Acute effect of fine and coarse particular matter on cardiovascular visits in Ningbo, China.

Although a growing number of epidemiological studies have been conducted on size-specific health effects of particulate matter in China, results remain inconsistent. In this study, we investigated acute effect of fine and coarse particular matter on cardiovascular hospital visits in Ningbo, China. We used generalized additive models to examine short-term effects of PM2.5 and PM10-2.5 on cardiovascular hospital visits by adjustment for temporal, seasonal, and meteorological effects. Subgroup analyses were conducted by age, sex, and season. We also examined the stability of their effects in multi-pollutant models. We found that PM2.5 were associated with cardiovascular hospital visits (RR = 1.006; 95% CI 1.000, 1.011) and results remained similar after adjustment for PM10-2.5 (RR = 1.005; 95% CI 0.998, 1.013). There was a borderline association between PM10-2.5 and cardiovascular hospital visits (RR = 1.007; 95% CI 0.997, 1.016), which disappeared after controlling for PM2.5 (RR = 1.000; 95% CI 0.988, 1.013). The associations appeared to be stronger in the cold season and among the elderly (≥ 75 years). The findings of this study suggested significant adverse effects of PM2.5, but no independent effects of PM10-2.5 on cardiovascular hospital visits. Additional studies are needed to confirm these findings.

Transcriptome analysis unravels spatiotemporal modulation of phytohormone-pathway expression underlying gibberellin-induced parthenocarpic fruit set in San Pedro-type fig (Ficus carica L.).

BACKGROUND: Gibberellin (GA) treatments can induce parthenocarpy in the main crop of San Pedro-type figs, the native non-parthenocarpic fruit, however, the underlying mechanism is still largely unclear. RESULTS: In our study, GA3 was applied to San Pedro-type fig main crop at anthesis. Sharply increased GA3 content was detected in both female flowers and receptacle, along with significantly decreased indole-3-acetic acid (IAA), zeatin and abscisic acid (ABA) levels in female flowers, and increased zeatin peak intensity and earlier ABA peak in receptacles. Transcriptome comparison between control and treatment groups identified more differentially expressed genes (DEGs) in receptacles than in female flowers 2 and 4 days after treatment (DAT); 10 DAT, the number of DEGs became similar in the two tissues. Synchronized changing trends of phytohormone-associated DEGs were observed in female flowers and receptacles with fruit development. Modulation of ethylene and GA signaling and auxin metabolism by exogenous GA3 occurred mainly 2 DAT, whereas changes in auxin, cytokinin and ABA signaling occurred mainly 10 DAT. Auxin-, ethylene- and ABA-metabolism and response pathways were largely regulated in the two tissues, mostly 2 and 10 DAT. The major components altering fig phytohormone metabolic and response patterns included downregulated GA2ox, BAS1, NCED and ACO, and upregulated ABA 8'-h and AUX/IAA. CONCLUSIONS: Thus GA-induced parthenocarpy in fig is co-modulated by the female flowers and receptacle, and repression of ABA and ethylene biosynthesis and GA catabolism might be the main forces deflecting abscission and producing fig parthenocarpy.

Air pollution and hospital visits for acute upper and lower respiratory infections among children in Ningbo, China: A time-series analysis.

Acute upper and lower respiratory infections are main causes of mortality and morbidity in children. Air pollution has been recognized as an important contributor to development and exacerbation of respiratory infections. However, few studies are available in China. In this study, we investigated the short-term effect of air pollution on hospital visits for acute upper and lower respiratory infections among children under 15 years in Ningbo, China. Poisson generalized models were used to estimate the associations between air pollution and hospital visits for acute upper and lower respiratory infections adjusted for temporal, seasonal, and meteorological effects. We found that four pollutants (PM2.5, PM10, NO2, and SO2) were significantly associated with hospital visits for acute upper and lower respiratory infections. The effect estimates for acute upper respiratory infections tended to be higher (PM2.5 ER = 3.46, 95% CI 2.18, 4.76; PM10 ER = 2.81, 95% CI 1.93, 3.69; NO2 ER = 11.27, 95% CI 8.70, 13.89; SO2 ER = 15.17, 95% CI 11.29, 19.19). Significant associations for gaseous pollutants (NO2 and SO2) were observed after adjustment for particular matter. Stronger associations were observed among older children and in the cold period. Our study suggested that short-term exposure to outdoor air pollution was associated with hospital visits for acute upper and lower respiratory infections in Ningbo.

Systemic Bioavailability and Dose Proportionality of Omega-3 Administered in Free Fatty Acid Form Compared With Ethyl Ester Form: Results of a Phase 1 Study in Healthy Volunteers.

BACKGROUND: Omega-3 carboxylic acids (OM3-CA) contains eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in free fatty acid form. Per gram, OM3-CA includes approximately half as much EPA as icosapent ethyl (IPE), an ethyl ester formulation of EPA. OBJECTIVE: The study aim was to assess systemic EPA and EPA + DHA exposures and plasma lipid parameters following multiple OM3-CA or IPE doses under low-fat dietary conditions, and dose proportionality after OM3-CA administration. METHODS: In this phase 1, two-cohort, open-label study (N = 114), participants following the Therapeutic Lifestyle Changes diet received either OM3-CA 2 g once daily for 10 days then OM3-CA 4 g once daily for 10 days, or IPE 2 g twice daily for 20 days. Exposure was considered similar if the 90% confidence intervals (CIs) of geometric least-squares mean (LSM) ratios for key pharmacokinetic parameters were within 80-125%. RESULTS: Baseline-adjusted steady-state EPA exposure was similar after dosing with OM3-CA 4 g/day versus IPE 4 g/day (LSM ratio, area under the concentration-time curve from time 0 to 24 h: 93.9%; 90% CI 85.6, 103.0). Combined molar-equivalent EPA + DHA exposure was 30.6% higher following OM3-CA 4 g/day than IPE 4 g/day. EPA and DHA exposure increased approximately proportionally with OM3-CA dose (2-4 g/day). Changes from baseline in lipid parameters were similar in the two cohorts. CONCLUSION: EPA exposure from OM3-CA and IPE was similar under low-fat dietary conditions, despite OM3-CA containing only approximately half as much EPA as IPE. EPA and DHA exposure from OM3-CA increased proportionally with dose.

Dietary supplementation of probiotic Bacillus PC465 isolated from the gut of Fenneropenaeus chinensis improves the health status and resistance of Litopenaeus vannamei against white spot syndrome virus.

This study conducted a 30-day feeding trial and a subsequent 20-day anti-virus infection trial to determine the effects of probiotic Bacillus PC465 on the growth, health status, and disease resistance of Litopenaeus vannamei. Shrimp samples were fed with three practical diets prepared from shrimp feed containing varying probiotic doses [0 (control), 10(7), and 10(9) CFU g(-1)]. Probiotic supplementation significantly increased the weight gain and survival of L. vannamei (p < 0.05). The effect of 10(9) CFU g(-1) on the growth rate was higher than that of 10(7) CFU g(-1). Compared with those in the control group, the activities of digestive enzymes, such as amylase, protease, and lipase, in the shrimp mid-gut significantly increased in the probiotic-fed groups on days 15 and 30, except lipase on day 30. The influence of 10(9) CFU g(-1) on enzyme activities was also greater than that of 10(7) CFU g(-1). Scanning electron microscopy revealed folds and large ravines across the interior surface of the mid-gut, and the number of these folds and ravines increased significantly after the probiotic was administered. The probiotic treatment significantly (p < 0.05) enhanced the transcription of penaeidin 3a (Pen-3a), peroxinectin, C-type lectin 3 (Lec-3), and thioredoxin (Trx) in the hemocytes of L. vannamei. Likewise, probiotic treatment increased the transcription of hemocyanin in the hepatopancreas of L. vannamei. The probiotic treatment also significantly increased the transcription of prophenoloxidase (proPO) but decreased the transcription of crustin in hemocytes. By contrast, the same treatment failed to increase the transcription of Ras-related protein (Rab-6) in hemocytes. The number of species and biomass of Bacillus in the mid-gut were higher in the probiotic-fed group than in the control group. The total biomass of microbes was higher in the shrimp fed with 10(7) CFU g(-1) than in the shrimp fed with 10(9) CFU g(-1) and the control group on days 15 and 30 post-feeding. In two white spot syndrome virus (WSSV) infections, the weight gain, survival, and WSSV copies within the gills of the probiotic-treated shrimp significantly differed (p < 0.05) from those of the control group. Relatively efficient protection was associated with probiotic feeding. Results suggested that Bacillus PC465 feeding improves the growth performance, survival, digestion, and nutrient absorption of L. vannamei. Probiotic treatment also enhances the microbial structures in the gut, promotes the immune status of shrimp, and provides protection against viral infection. The supplementation with 10(9) CFU g(-1) can also improve the growth and survival of L. vannamei.

GSE1 negative regulation by miR-489-5p promotes breast cancer cell proliferation and invasion.

Gse1 coiled-coil protein (GSE1), also known as KIAA0182, is a proline rich protein. However, the function of GSE1 is largely unknown. In this study, we reported that GSE1 is overexpression in breast cancer and silencing of GSE1 significantly suppressed breast cancer cells proliferation, migration and invasion. Furthermore, GSE1 was identified as a direct target of miR-489-5p, which is significantly reduced in breast cancer tissues. In addition, forced expression of miR-489-5p suppressed breast cancer cells proliferation, migration and invasion. Moreover, depletion of GSE1 by siRNAs significantly abrogated the enhanced proliferation, migration and invasion of breast cancer cells consequent to miR-489-5p depletion. Taken together, these findings suggest that GSE1 may function as a novel oncogene in breast cancer and it can be regulated by miR-489-5p.

Growth and lipid accumulation characteristics of Scenedesmus obliquus in semi-continuous cultivation outdoors for biodiesel feedstock production.

In an effort to identify suitable microalgal species for biodiesel production, seven species were isolated from various habitats and their growth characteristics were compared. The results demonstrated that a green alga Scenedesmus obliquus could grow more rapidly and synthesize more lipids than other six microalgal strains. S. obliquus grew well both indoors and outdoors, and reached higher µmax indoors than that outdoors. However, the cells achieved higher dry weight (4.36 g L(-1)), lipid content (49.6%) and productivity (183 mg L(-1) day(-1)) outdoors than in indoor cultures. During the 61 days semi-continuous cultivation outdoors, high biomass productivities (450-550 mg L(-1) day(-1)) and µmax (1.05-1.44 day(-1)) were obtained. The cells could also achieve high lipid productivities (151-193 mg L(-1) day(-1)). These results indicated that S. obliquus was promising for lipids production in semi-continuous cultivation outdoors.