Breaking the in-coupling efficiency limit in waveguide-based AR displays with polarization volume gratings.

Augmented reality (AR) displays, heralded as the next-generation platform for spatial computing, metaverse, and digital twins, empower users to perceive digital images overlaid with real-world environment, fostering a deeper level of human-digital interactions. With the rapid evolution of couplers, waveguide-based AR displays have streamlined the entire system, boasting a slim form factor and high optical performance. However, challenges persist in the waveguide combiner, including low optical efficiency and poor image uniformity, significantly hindering the long-term usage and user experience. In this paper, we first analyze the root causes of the low optical efficiency and poor uniformity in waveguide-based AR displays. We then discover and elucidate an anomalous polarization conversion phenomenon inherent to polarization volume gratings (PVGs) when the incident light direction does not satisfy the Bragg condition. This new property is effectively leveraged to circumvent the tradeoff between in-coupling efficiency and eyebox uniformity. Through feasibility demonstration experiments, we measure the light leakage in multiple PVGs with varying thicknesses using a laser source and a liquid-crystal-on-silicon light engine. The experiment corroborates the polarization conversion phenomenon, and the results align with simulation well. To explore the potential of such a polarization conversion phenomenon further, we design and simulate a waveguide display with a 50° field of view. Through achieving first-order polarization conversion in a PVG, the in-coupling efficiency and uniformity are improved by 2 times and 2.3 times, respectively, compared to conventional couplers. This groundbreaking discovery holds immense potential for revolutionizing next-generation waveguide-based AR displays, promising a higher efficiency and superior image uniformity.

Simulation of gradient period polarization volume gratings for augmented reality displays.

Augmented reality (AR) displays are gaining attention as next-generation intelligent display technologies. Diffractive waveguide technologies are progressively becoming the AR display industry's preferred option. Gradient period polarization volume holographic gratings (PVGs), which are considered to have the potential to expand the field of view (FOV) of waveguide display systems due to their wide bandwidth diffraction characteristics, have been proposed as coupling elements for diffraction waveguide systems in recent years. Here, what we believe to be a novel modeling method for gradient period PVGs is proposed by incorporating grating stacking and scattering analysis utilizing rigorous coupled-wave analysis (RCWA) theory. The diffraction efficiency and polarization response were extensively explored using this simulation model. In addition, a dual-layer full-color diffractive waveguide imaging simulation using proposed gradient period PVGs is accomplished in Zemax software using a self-compiled dynamic link library (DLL), achieving a 53° diagonal FOV at a 16:9 aspect ratio. This work furthers the development of PVGs by providing unique ideas for the field of view design of AR display.

The dynamic molecular characteristics of neutrophils are associated with disease progression in dengue patients.

Dengue, the most prevalent mosquito-borne disease worldwide, poses a significant health burden. This study integrates clinical data and transcriptomic datasets from different phases of dengue to investigate distinctive and shared cellular and molecular features. Clinical data from 29 dengue patients were collected and analyzed alongside a public transcriptomic data set (GSE28405) to perform differential gene expression analysis, functional enrichment, immune landscape assessment, and development of machine learning model. Neutropenia was observed in 54.79% of dengue patients, particularly during the defervescence phase (65.79%) in clinical cohorts. Bioinformatics analyses corroborated a significant reduction in neutrophil immune infiltration in dengue patients. Receiver operating characteristic curve analysis demonstrated that dynamic changes in neutrophil infiltration levels could predict disease progression, especially during the defervescence phase, with the area under the curve of 0.96. Three neutrophil-associated biomarkers-DHRS12, Transforming growth factor alpha, and ZDHHC19-were identified as promising for diagnosing and predicting dengue progression. In addition, the activation of neutrophil extracellular traps was significantly enhanced and linked to FcγR-mediated signaling pathways and Toll-like receptor signaling pathways. Neutrophil activation and depletion play a critical role in dengue's immune response. The identified biomarkers and their associated pathways offer potential for improved diagnosis and understanding of dengue pathogenesis and progression.

Viral and antibody dynamics of acute infection with SARS-CoV-2 omicron variant (B.1.1.529): a prospective cohort study from Shenzhen, China.

BACKGROUND: Elucidating viral dynamics within the host is important for designing public health measures against SARS-CoV-2, particularly during the early stages of infection when transmission potential rapidly increases. We aimed to analyse the viral and antibody dynamics of the omicron variant in relation to symptom onset or laboratory confirmation and replication dynamics throughout the infection course. METHODS: In this prospective cohort study, patients with laboratory-confirmed SARS-CoV-2 infection who were admitted to Shenzhen Third People's Hospital (Shenzhen, China) between Jan 11, 2020, and April 24, 2022, were screened for eligibility. We included immunocompetent individuals with acute SARS-CoV-2 infection without antiviral agents targeting SARS-CoV-2. Serial nasopharyngeal swabs and plasma samples were analysed for viral RNAs and specific IgG antibodies of SARS-CoV-2. The comparative viral and antibody kinetics in association with symptom onset or laboratory confirmation and replication dynamics throughout the infection course were calculated by the locally estimated scatterplot smoothing curve fitting polynomial regression. The associations between viral and antibody dynamics and vaccination, age, sex, disease severity, and underlying health conditions were analysed using the Mann-Whitney U test and the Gehan-Breslow-Wilcoxon method. FINDINGS: 15 406 serial nasopharyngeal swabs and 2324 plasma samples were taken from 2043 individuals with acute SARS-CoV-2 infection (n=217 prototype [A.1] and D614G [B.1] variant [wild-type]; n=105 delta variant [B.1.617.2]; n=1721 omicron variant [B.1.1.529]) and were included for the analyses. The mean Ct value of omicron variant on the first day post symptom onset (dpo; defined as the first day post laboratory confirmation in asymptomatic participants) was 22·65 (95% CI 22·05-23·26). Peak viral load was reached with a mean Ct value of 17·63 (17·47-17·79) at a mean of 3·19 dpo (95% CI 3·09-3·28), and viral clearance (Ct values ≥35) was reached at a mean of 13·50 dpo (95% CI 13·32-13·67). Omicron variant showed faster viral replication and clearance than wild-type SARS-CoV-2 and delta variant, and the viral load at the first dpo and the peak viral load was lower than delta variant but higher than wild-type SARS-CoV-2. Age, sex, disease severity, and underlying health conditions were associated with the viral dynamics of omicron variant, with faster viral clearance found in young (aged 0-14 years), male, and asymptomatic participants, and those without underlying health conditions. Replication dynamics thoughout the infection course showed that peak viral load was reached at a mean of 5·06 dpo (4·76-5·36) and viral clearance took a mean of 14·27 days (13·6-14·93) for omicron variant. SARS-CoV-2-specific IgG increased earlier and faster to significantly higher concentrations in breakthrough infection than naive infection with omicron variant, despite long intervals (≥7 months) between the last dose of vaccination and infection. INTERPRETATION: Our data provide a comprehensive overview of the longitudinal viral and antibody dynamics of omicron variant in people with acute SARS-CoV-2 infection, with important implications for public health strategies, including population screening, antiviral treatment, isolation periods, and vaccination. FUNDING: National Natural Science Foundation of China and Emergency Key Program of Guangzhou Laboratory. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

High-efficiency and compact two-dimensional exit pupil expansion design for diffractive waveguide based on polarization volume grating.

We propose a two-dimensional exit pupil expansion (2D-EPE) design of a diffractive waveguide (DW) based on polarization volume grating (PVG). The designed waveguide structure and pupil expansion principle are introduced in this paper. The light propagation behavior and available field of view (FoV) of the proposed waveguide are investigated by simulations. In addition, the waveguide sample based on the proposed design is prepared, and an imaging system based on a monochromatic MicroLED projector is built for AR imaging experiments. The experimental results show that the prepared waveguide system can achieve a clear AR display with a diagonal FoV of 30° and obtain an exit pupil magnification of nearly 20 times compared to the entrance pupil size. The optical imaging efficiency was measured to be 3.85%, and the backward light leakage rate was as low as 8.7%. This work further enhances the feasibility and practicality of the PVG-waveguide technology and provides a promising candidate for AR-DW applications.

Cladophora can mitigate the shock of glyphosate-containing wastewater on constructed wetlands coupled with microbial fuel cells.

This study investigated the performance of constructed wetlands coupled with microbial fuel cells (CW-MFCs) treating agricultural wastewater containing glyphosate (N-phosphonomethyl glycine, PMG), and the use of Cladophora as a cathode plant in this system. Ten devices were divided into Cladophora groups (CGs) and no Cladophora groups (NGs), with five PMG concentrations (0, 10, 25, 50, and 100 mg/L). PMG removal efficiency significantly decreased with increasing PMG (P < 0.01) and was higher in CG devices than in NG devices at low PMG concentrations (<50 mg/L). The removal efficiency of chemical oxygen demand (COD) and NH4+ in CGs was significantly higher than in NGs (P < 0.01). The highest power densities of 6.37 (CGs) and 6.26 mW/m2 (NGs) were obtained at 50 mg/L PMG, and the average voltage was significantly higher in CGs than in NGs (p < 0.01). Moreover, PMG had a negative effect on the enrichment of electrochemically active bacteria, but Cladophora could mitigate this effect. The abundance of the resistance gene epsps was stabilized; The phnJ gene increased with increasing PMG in NGs and was downregulated at high PMG concentration in CGs, indicating better microbial adaptation to PMG in CGs throughout the experiment.

Diagnostic Value and Clinical Application of mNGS for Post-Liver Transplantation Infection: A Cross-Sectional Study With Case Reports.

Liver transplantation is widely acknowledged as the only effective treatment for end-stage liver disease, and infection is reportedly an important cause of postoperative death. Clinical use of metagenomic next-generation sequencing (mNGS) to diagnose postoperative infection and successfully guide drug therapy remains rare. This study included patients with infectious complications after liver transplantation from July 2019 to December 2020 and was divided into three groups: pneumonia, unknown fever, and others (including hepatic failure, kidney failure, cirrhosis after LT, and other postoperative complications that predispose to infection). The mNGS sequencing was used to detect microorganisms, and the results were compared with traditional culture. We found that mNGS yielded improved sensitivity over culture (85.19 vs. 22.22%; p<0.0001) but lower specificity (35.71 vs. 89.28%; p<0.0001). Among the 48 kinds of pathogens detected, the Torque teno virus 22 (15/122) was the most common, followed by Primate erythroparvovirus 1 (13/122). The top four bacteria included Klebsiella pneumoniae (n = 8), Enterococcus faecium (n = 5), Stenotrophomonas maltophilia (n = 4), and Escherichia coli (n = 4). Aspergillus fumigatus was the most common fungus. The bronchoalveolar lavage fluid (BALF) exhibited the highest proportion of positive findings among sample types, with viral, fungal, and bacterial mixed infection being the most common (n = 6, 19.35%). Besides, using mNGS for early diagnosis of infection after liver transplantation may effectively prolong patient survival. This is the first study to explore the application value of mNGS and its comparison with traditional culture in pneumonia and other infections in post-liver transplantation patients. The simultaneous application of these two methods suggested that the Torque teno virus 22, Klebsiella pneumoniae, and the Aspergillus fumigatus are the most common pathogens of viruses, bacteria, and fungi after LT, suggesting that these pathogens may be associated with postoperative pathogen infection and patient prognosis. The mNGS technique showed distinct advantages in detecting mixed, viral, and parasitic infections in this patient population. Further studies are warranted to systematically elucidate the dynamic evolution and molecular characteristics of infection after liver transplantation.

Catechins as a Potential Dietary Supplementation in Prevention of Comorbidities Linked with Down Syndrome.

Plant-derived polyphenols flavonoids are increasingly being recognized for their medicinal potential. These bioactive compounds derived from plants are gaining more interest in ameliorating adverse health risks because of their low toxicity and few side effects. Among them, therapeutic approaches demonstrated the efficacy of catechins, a major group of flavonoids, in reverting several aspects of Down syndrome, the most common genomic disorder that causes intellectual disability. Down syndrome is characterized by increased incidence of developing Alzheimer's disease, obesity, and subsequent metabolic disorders. In this focused review, we examine the main effects of catechins on comorbidities linked with Down syndrome. We also provide evidence of catechin effects on DYRK1A, a dosage-sensitive gene encoding a protein kinase involved in brain defects and metabolic disease associated with Down syndrome.

Long non-coding RNA LINC01123 promotes cell proliferation, migration and invasion via interacting with SRSF7 in colorectal cancer.

BACKGROUND: Increasing evidences demonstrated that long non-coding RNAs (lncRNAs) participates in the occurrence and development of cancer. In this study, we explored the function and molecular mechanism of LINC01123 in colorectal cancer progression. METHODS: Analyze the expression level of LINC01123 in gastrointestinal tumors via TCGA database. Colorectal tumor tissues and normal tissues were collected to detect the expression of LINC01123 by RT-qPCR. CCK-8 assay, clone formation assay, transwell assay, and wound healing assays were used to explore the effects of LINC01123 on the proliferation, invasion and migration of colorectal cancer cells. Coomassie blue staining, RNA pull-down and mass spectrometry were used to screen the protein interacted with LINC01123. Xenograft model was used to explore the effect of LINC01123 in vivo. RESULTS: LINC01123 was up-regulated in colorectal cancer tumor tissues. The proliferation, invasion and migration ability of colorectal cancer cells were decreased significantly after LINC01123 knockdown, and it may inhibit its expression by interacted with SRSF7, thereby promoting colorectal cancer progression. CONCLUSIONS: LINC01123 can promote the proliferation, invasion and migration of colorectal cancer cells by regulating SRSF7, suggesting that it may be an important regulator of colorectal cancer progression.

Realizing the imaging simulation of reflective polarization volume gratings.

Near-eye holographic waveguide display system using novel reflective polarized volume gratings (RPVG) have lately gotten a lot of interest. However, from polarization characteristics to imaging simulation, there is no systematic approach based on RPVG. Here, a full methodology for solving this problem using the rigorous coupled wave analysis (RCWA) model is presented. This self-built RCWA model is used to examine the optical behavior of RPVG. This excellent portability of the RCWA model makes it possible for RPVG as a diffractive optical element, which is integrated into the commercial optical software Zemax via a self-compiled dynamic link library (DLL), and a full-color imaging simulation of the based-RPVG waveguide display system is obtained. Our work provides an instructive imaging analysis method using the RPVG for holographic waveguide display.

Cytokine/Chemokine Expression Is Closely Associated Disease Severity of Human Adenovirus Infections in Immunocompetent Adults and Predicts Disease Progression.

Increasing human Adenovirus (HAdV) infections complicated with acute respiratory distress syndrome (ARDS) even fatal outcome were reported in immunocompetent adolescent and adult patients. Here, we characterized the cytokine/chemokine expression profiles of immunocompetent patients complicated with ARDS during HAdV infection and identified biomarkers for disease severity/progression. Forty-eight cytokines/chemokines in the plasma samples from 19 HAdV-infected immunocompetent adolescent and adult patients (ten complicated with ARDS) were measured and analyzed in combination with clinical indices. Immunocompetent patients with ARDS caused by severe acute respiratory disease coronavirus (SARS-CoV)-2, 2009 pandemic H1N1 (panH1N1) or bacteria were included for comparative analyses. Similar indices of disease course/progression were found in immunocompetent patients with ARDS caused by HAdV, SARS-CoV-2 or panH1N infections, whereas the HAdV-infected group showed a higher prevalence of viremia, as well as increased levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and creatine kinase (CK). Expression levels of 33 cytokines/chemokines were increased significantly in HAdV-infected patients with ARDS compared with that in healthy controls, and many of them were also significantly higher than those in SARS-CoV-2-infected and panH1N1-infected patients. Expression of interferon (IFN)-γ, interleukin (IL)-1ß, hepatocyte growth factor (HGF), monokine induced by IFN-γ (MIG), IL-6, macrophage-colony stimulating factor (M-CSF), IL-10, IL-1α and IL-2Ra was significantly higher in HAdV-infected patients with ARDS than that in those without ARDS, and negatively associated with the ratio of the partial pressure of oxygen in arterial blood/fraction of inspired oxygen (PaO2/FiO2). Analyses of the receiver operating characteristic curve (ROC) showed that expression of IL-10, M-CSF, MIG, HGF, IL-1ß, IFN-γ and IL-2Ra could predict the progression of HAdV infection, with the highest area under the curve (AUC) of 0.944 obtained for IL-10. Of note, the AUC value for the combination of IL-10, IFN-γ, and M-CSF reached 1. In conclusion, the "cytokine storm" occurred during HAdV infection in immunocompetent patients, and expression of IL-10, M-CSF, MIG, HGF, IL-1ß, IFN-γ and IL-2Ra was closely associated with disease severity and could predict disease progression.

Effect of drought on photosynthesis, total antioxidant capacity, bioactive component accumulation, and the transcriptome of Atractylodes lancea.

BACKGROUND: Atractylodes lancea (Thunb.) DC, a medicinal herb belonging to the Asteraceae family, often faces severe drought stress during its growth. Until now, there has been no research on the effect of drought stress on the quality formation of A. lancea. Therefore, the present study aimed to study the effects of drought stress on A. lancea through physical and chemical analysis, and to reveal the related molecular mechanisms via transcriptome analysis. RESULTS: The photosynthesis was markedly inhibited under drought stress. There were alterations to photosynthetic parameters (Pn, Gs, Ci) and chlorophyll fluorescence (Fv/Fm, NPQ), and the chlorophyll content decreased. Twenty genes encoding important regulatory enzymes in light and dark reactions, including the Rubisco gene of the Calvin cycle, were significantly downregulated. After exposure to drought stress for more than 4 days, the activities of four antioxidative enzymes (SOD, POD CAT and APX) began to decrease and continued to decrease with longer stress exposure. Meanwhile, most of the genes encoding antioxidative enzymes were downregulated significantly. The downregulation of 21 genes related to the respiratory electron transport chain indicated that the blocked electron transfer accelerated excessive ROS. The MDA content was significantly elevated. The above data showed that 15 days of drought stress caused serious oxidative damage to A. lancea. Drought stress not only reduced the size and dry weight of A. lancea, but also lowered the amount of total volatile oil and the content of the main bioactive components. The total volatile oil and atractylodin content decreased slightly, whereas the content of atractylon and ß-eudesmol decreased significantly. Moreover, ten significantly downregulated genes encoding sesquiterpene synthase were mainly expressed in rhizomes. CONCLUSIONS: After exposed to drought stress, the process of assimilation was affected by the destruction of photosynthesis; stress tolerance was impaired because of the inhibition of the antioxidative enzyme system; and bioactive component biosynthesis was hindered by the downregulation of sesquiterpene synthase-related gene expression. All these had negative impacts on the quality formation of A. lancea under drought stress.

[Long non-coding RNA LINC01106 regulates colorectal cancer cell proliferation and apoptosis through the STAT3 pathway].

OBJECTIVE: To investigate the expression of LINC01106 in colorectal cancer and its role in regulating the proliferation and apoptosis of colorectal cancer cells. METHODS: We analyzed the data of LINC01106 expression levels in tumor tissues and normal tissues of patients with colorectal cancer in TCGA database and explored the association of LINC01106 expression level with the prognosis of the patients. Colorectal cancer SW480 cell lines with LINC01106 knockdown or overexpression were established, and their proliferation and apoptosis relative to the parental cells were evaluated using CCK-8 assay and flow cytometry, respectively. The expressions of p-STAT3, STAT3, and Bcl-2 in the cells were detected by immunoblotting. Nude mouse models bearing xenografts of SW480 cells with LINC01106 knockdown or na?ve SW480 cells were established to observe the effect of LINC01106 knockdown on the growth of SW480 cells in vivo. RESULTS: Analysis of the data from TCGA database showed that the expression level of LINC01106 was significantly higher in colorectal cancer tissues than in normal tissues, and LINC01106 expression level was significantly related to the prognosis of the patients (P < 0.05). Knockdown of LINC01106 significantly inhibited the proliferation and promoted apoptosis of SW480 cells (P < 0.05), while LINC01106 overexpression significantly promoted proliferation of the cells. LINC01106 knockdown in SW-480 cells obviously lowered the expressions of p- STAT3 and Bcl-2 and suppressed the growth of the xenograft in nude mice. CONCLUSIONS: LINC01106 is significantly up-regulated in colorectal cancer tissue and is related to the prognosis of the patients. LINC01106 can regulate the proliferation and apoptosis of SW480 cells through STAT3/Bcl-2 signaling and may serve as a potential marker for the diagnosis and prognostic evaluation of colorectal cancer.

Overview of the STAT-3 signaling pathway in cancer and the development of specific inhibitors.

Signal transducer and activator of transcription (STAT) proteins represent novel therapeutic targets for the treatment of cancer. In particular, STAT-3 serves critical roles in several cellular processes, including the cell cycle, cell proliferation, cellular apoptosis and tumorigenesis. Persistent activation of STAT-3 has been reported in a variety of cancer types, and a poor prognosis of cancer may be associated with the phosphorylation level of STAT-3. Furthermore, elevated STAT-3 activity has been demonstrated in a variety of mammalian cancers, both in vitro and in vivo. This indicates that STAT-3 serves an important role in the progression of numerous cancer types. A significant obstacle in developing STAT-3 inhibitors is the demonstration of the antitumor efficacy in in vivo systems and the lack of animal models for human tumors. Therefore, it is crucial to determine whether available STAT-3 inhibitors are suitable for clinical trials. Moreover, further preclinical studies are necessary to focus on the impact of STAT-3 inhibitors on tumor cells. When considering STAT-3 hyper-activation in human cancer, selective targeting to these proteins holds promise for significant advancement in cancer treatment. In the present study, advances in our knowledge of the structure of STAT-3 protein and its regulatory mechanisms are summarized. Moreover, the STAT-3 signaling pathway and its critical role in malignancy are discussed, in addition to the development of STAT-3 inhibitors in various cancer types.

Molecular Rescue of Dyrk1A Overexpression Alterations in Mice with Fontup® Dietary Supplement: Role of Green Tea Catechins.

Epigallocatechin gallate (EGCG) is an inhibitor of DYRK1A, a serine/threonine kinase considered to be a major contributor of cognitive dysfunctions in Down syndrome (DS). Two clinical trials in adult patients with DS have shown the safety and efficacy to improve cognitive phenotypes using commercial green tea extract containing EGCG (45% content). In the present study, we performed a preclinical study using FontUp®, a new nutritional supplement with a chocolate taste specifically formulated for the nutritional needs of patients with DS and enriched with a standardized amount of EGCG in young mice overexpressing Dyrk1A (TgBACDyrk1A). This preparation is differential with previous one used, because its green tea extract has been purified to up 94% EGCG of total catechins. We analyzed the in vitro effect of green tea catechins not only for EGCG, but for others residually contained in FontUp®, on DYRK1A kinase activity. Like EGCG, epicatechin gallate was a noncompetitive inhibitor against ATP, molecular docking computations confirming these results. Oral FontUp® normalized brain and plasma biomarkers deregulated in TgBACDyrk1A, without negative effect on liver and cardiac functions. We compared the bioavailability of EGCG in plasma and brain of mice and have demonstrated that EGCG had well crossed the blood-brain barrier.

Small molecule STAT3 inhibitor, 6Br-6a suppresses breast cancer growth in vitro and in vivo.

Signal transducer and activator of transcription 3 (STAT3) protein frequently overexpressed in many malignancies and plays an essential role in regulating proliferation, apoptosis, migration and invasion in cancer cells. However, No STAT3 inhibitor was used clinically. In this study, we evaluated the toxic potential of a novel STAT3 inhibitor, 6Br-6a in breast cancer cell lines. The anti-cancer effect and underlying mechanism of 6Br-6a on MDA-MB-231 and MCF-7 cells were determined in vitro and in xenograft mouse model. Our data demonstrated that 6Br-6a significantly induced cell cycle arrest and cell apoptosis in breast cancer via blocking the activation of STAT3. Finally, we verified these inhibitory effects of 6Br-6a in the MDA-MB-231 xenograft mouse model. In conclusion, 6Br-6a effectively inhibited activation of STAT3 and induced cell cycle arrest and apoptosis via regulating cyclin D1 and Bcl-2 expression. All of these data indicate that 6Br-6a could be a potential candidate for the treatment of breast cancer.

Methyl jasmonate promote protostane triterpenes accumulation by up-regulating the expression of squalene epoxidases in Alisma orientale.

Protostane triterpenes, which are found in Alisma orientale, are tetracyclic triterpenes with distinctive pharmacological activities. The natural distribution of protostane triterpenes is limited mainly to members of the botanical family Alismataceae. Squalene epoxidase (SE) is the key rate-limiting enzyme in triterpene biosynthesis. In this study, we report the characterization of two SEs from A. orientale. AoSE1 and AoSE2 were expressed as fusion proteins in E. coli, and the purified proteins were used in functional research. In vitro enzyme assays showed that AoSE1 and AoSE2 catalyze the formation of oxidosqualene from squalene. Immunoassays revealed that the tubers contain the highest levels of AoSE1 and AoSE2. After MeJA induction, which is the main elicitor of triterpene biosynthesis, the contents of 2,3-oxidosqualene and alisol B 23-acetate increased by 1.96- and 2.53-fold, respectively. In addition, the expression of both AoSE proteins was significantly increased at four days after MeJA treatment. The contents of 2,3-oxidosqualene and alisol B 23-acetate were also positively correlated with AoSEs expression at different times after MeJA treatment. These results suggest that AoSE1 and AoSE2 are the key regulatory points in protostane triterpenes biosynthesis, and that MeJA regulates the biosynthesis of these compounds by increasing the expression of AoSE1 and AoSE2.

High expression of apoptosis protein (Api-5) in chemoresistant triple-negative breast cancers: an innovative target.

Anti-apoptotic protein-5 (API-5) is a survival protein interacting with the protein acinus, preventing its cleavage by caspase-3 and thus inhibiting apoptosis. We studied the effect of targeting API-5 in chemoresistant triple negative breast cancers (TNBCs), to reverse chemoresistance. 78 TNBC biopsies from patients with different responses to chemotherapy were analysed for API-5 expression before any treatment. Further studies on API-5 expression and inhibition were performed on patient-derived TNBC xenografts, one highly sensitive to chemotherapies (XBC-S) and the other resistant to most tested drugs (XBC-R). In situ assessments of necrosis, cell proliferation, angiogenesis, and apoptosis in response to anti-API-5 peptide were performed on the TNBC xenografts. Clinical analyses of the 78 TNBC biopsies revealed that API-5 was more markedly expressed in endothelial cells before any treatment among patients with chemoresistant TNBC, and this was associated with greater micro-vessel density. A transcriptomic analysis of xenografted tumors showed an involvement of anti-apoptotic genes in the XBC-R model, and API-5 expression was higher in XBC-R endothelial cells. API-5 expression was also correlated with hypoxic stress conditions both in vitro and in vivo. 28 days of anti-API-5 peptide efficiently inhibited the XBC-R xenograft via caspase-3 apoptosis. This inhibition was associated with major inhibition of angiogenesis associated with necrosis and apoptosis. API-5 protein could be a valid therapeutic target in chemoresistant metastatic TNBC.

Identifying resurrection genes through the differentially expressed genes between Selaginella tamariscina (Beauv.) spring and Selaginella moellendorffii Hieron under drought stress.

Selaginella tamariscina (Beauv.) spring, a primitive vascular resurrection plant, can survive extreme drought and recover when water becomes available. To identify drought-inducible genes and to clarify the molecular mechanism of drought tolerance, a comparative transcriptional pattern analysis was conducted between S. tamariscina and Selaginella moellendorffii Hieron (drought sensitive). 133 drought related genes were identified, including 72 functional genes and 61 regulatory genes. And several drought responsive reactions, such as antioxidant activity, osmotic balance, cuticle defense and signal transduction were highlighted in S. tamariscina under drought. Notably, besides peroxidase, catalase and L-ascorbate oxidase genes, DEGs associated with phenylalanine metabolism and polyamine catabolism could be alternative ways to enhance antioxidant ability in S. tamariscina. DEGs related to soluble carbohydrate metabolism, late embryogenesis abundant protein (LEA) and aquaporin protein (AQP) confirmed that osmotic adjustment could resist drought during desiccation. DEGs involved in xyloglucan metabolic process, pectin metabolic process and cutin biosynthesis may also contribute to drought tolerance of S. tamariscina by cuticle defense. Drought-responsive genes encoding protein kinases, calcium sensors, transcription factors (TFs) and plant hormones also help to drought resistance of S. tamariscina. The preliminary validation experiments were performed and the results were consistent with our hypothetical integrated regulatory network. The results of this study provide candidate resurrection genes and an integrated regulatory network for further studies on the molecular mechanisms of stress tolerance in S. tamariscina.