Simultaneous production of biosurfactant and extracellular unspecific peroxygenases by Moesziomyces aphidis XM01 enables an efficient strategy for crude oil degradation.

Crude oil is a hazardous pollutant that poses significant and lasting harm to human health and ecosystems. In this study, Moesziomyces aphidis XM01, a biosurfactant mannosylerythritol lipids (MELs)-producing yeast, was utilized for crude oil degradation. Unlike most microorganisms relying on cytochrome P450, XM01 employed two extracellular unspecific peroxygenases, MaUPO.1 and MaUPO.2, with preference for polycyclic aromatic hydrocarbons (PAHs) and n-alkanes respectively, thus facilitating efficient crude oil degradation. The MELs produced by XM01 exhibited a significant emulsification activity of 65.9% for crude oil and were consequently supplemented in an "exogenous MELs addition" strategy to boost crude oil degradation, resulting in an optimal degradation ratio of 72.3%. Furthermore, a new and simple "pre-MELs production" strategy was implemented, achieving a maximum degradation ratio of 95.9%. During this process, the synergistic up-regulation of MaUPO.1, MaUPO.1 and the key MELs synthesis genes contributed to the efficient degradation of crude oil. Additionally, the phylogenetic and geographic distribution analysis of MaUPO.1 and MaUPO.1 revealed their wide occurrence among fungi in Basidiomycota and Ascomycota, with high transcription levels across global ocean, highlighting their important role in biodegradation of crude oil. In conclusion, M. aphidis XM01 emerges as a novel yeast for efficient and eco-friendly crude oil degradation.

Unraveling the relationship between audience engagement and audiovisual characteristics of automotive green advertising on Chinese TikTok (Douyin).

As video platforms such as Douyin, also known as TikTok's Chinese version, continue to grow, there is an increasing interest in the study of green advertising videos to understand their audiovisual features and their impact on audience engagement. In this research, we specifically focus on green advertising within the automotive industry. Drawing on literature from sustainability, green advertising, and communication studies, we identified seven audiovisual aspects and three persuasive strategies pertinent to green automotive advertising videos. Utilizing a mixed-methods video analysis framework, we analyzed a dataset of 2,553 green automotive advertising videos on Douyin over three years from 15 June 2020 to 15 June 2023. These videos exhibited higher loudness, a faster pace, and longer durations compared to their non-green counterparts. We categorized three distinct types of green advertising videos on Douyin and established that specific audiovisual features and persuasive strategies are significantly correlated with audience engagement levels. This study not only delineates the audiovisual characteristics of green automotive advertising in China's digital space but also contributes to the broader discourse on sustainable marketing practices on social networks like TikTok. The findings extend image-centric research to video content and provide marketers with data-driven insights for crafting effective content creation strategies on Douyin.

Acquired Multidrug Resistance in AML Is Caused by Low Apoptotic Priming in Relapsed Myeloblasts.

In many cancers, mortality is associated with the emergence of relapse with multidrug resistance (MDR). Thus far, the investigation of cancer relapse mechanisms has largely focused on acquired genetic mutations. Using acute myeloid leukemia (AML) patient-derived xenografts (PDX), we systematically elucidated a basis of MDR and identified drug sensitivity in relapsed AML. We derived pharmacologic sensitivity for 22 AML PDX models using dynamic BH3 profiling (DBP), together with genomics and transcriptomics. Using in vivo acquired resistant PDXs, we found that resistance to unrelated, narrowly targeted agents in distinct PDXs was accompanied by broad resistance to drugs with disparate mechanisms. Moreover, baseline mitochondrial apoptotic priming was consistently reduced regardless of the class of drug-inducing selection. By applying DBP, we identified drugs showing effective in vivo activity in resistant models. This study implies evasion of apoptosis drives drug resistance and demonstrates the feasibility of the DBP approach to identify active drugs for patients with relapsed AML. SIGNIFICANCE: Acquired resistance to targeted therapy remains challenging in AML. We found that reduction in mitochondrial priming and common transcriptomic signatures was a conserved mechanism of acquired resistance across different drug classes in vivo. Drugs active in vivo can be identified even in the multidrug resistant state by DBP.

Derivation and External Validation of the Ottawa Bloodstream Infection Model for Acutely Ill Adults.

BACKGROUND: Knowing the probability that patients have a bloodstream infection (BSI) could influence the ordering of blood cultures and interpretation of their preliminary results. Many previous BSI probability models have limited applicability and accuracy. This study used currently recommended modeling techniques and a large sample to derive and validate the Ottawa BSI Model. METHODS: At a tertiary care teaching hospital, we retrieved a random sample of 4180 adults having blood cultures in our emergency department or during the initial 48 h of the encounter. Variable selection was based on clinical experience and a systematic review of previous model performance. Model performance was measured in a temporal external validation group of 4680 patients. RESULTS: A total of 327 derivation patients had a BSI (8.0%). BSI risk increased with increased number of culture sets (2 sets: adjusted odds ratio [aOR] 1.52 [1.10-2.11]; 3 sets: 1.99 [0.86-4.58]); with indwelling catheter (aOR 2.07 [1.34-3.20); with increasing temperature, heart rate, and neutrophil-lymphocyte ratio; and with decreasing systolic blood pressure, platelet count, urea-creatinine ratio, and estimated glomerular filtration rate. In the temporal external validation group, model discrimination was good (c-statistic 0.71 [0.69-0.74]) and calibration was very good (integrated calibration index .016 [.010-.024]). Exclusion of validation patients with acute SARS-CoV-2 infection improved discrimination slightly (c-statistic 0.73 [0.69-0.76]). CONCLUSIONS: The Ottawa BSI Model uses commonly available data to return an expected BSI probability for acutely ill patients. However, it cannot exclude BSI and its complexity requires computational assistance to use.

Ce3+-Eu2+ Co-doped BaCa13Mg2(SiO4)8 cyan phosphor-ultra-high energy transfer efficiency for white light emitting diodes.

The energy transfer of Ce3+-Eu2+ can often greatly increase the luminescence efficiency and expand the scope of application. In this study, blue to cyan color-tunable phosphors BaCa13Mg2(SiO4)8:Ce3+,Eu2+ were prepared. BaCa13Mg2(SiO4)8:Eu2+ cyan phosphors have limited applications in WLEDs because of their disadvantages, including the inadequate luminescence performance and imperfect matching of UV chips. Therefore, Ce3+ ions were used as sensitizers to enhance the optical performance of Eu2+ ions. The energy transfer efficiency between Ce3+ and Eu2+ in the BaCa13Mg2(SiO4)8 host was calculated to be 96.7%, and the incorporation of Ce3+ ions boosted the integrated intensity and quantum efficiency of the emission spectrum by approximately 80% and 20%, respectively. At 140 °C, the integral emission intensities could still keep at 81.5% of the initial integral intensities at 25 °C. The Ce3+, Eu2+ co-doped cyan phosphor-based WLED lamp could produce outstanding warm white light with CIE coordinates of (0.3722, 0.3222), demonstrating the enormous potential for WLED applications.

PPM1D modulates hematopoietic cell fitness and response to DNA damage and is a therapeutic target in myeloid malignancy.

PPM1D encodes a phosphatase that is recurrently activated across cancer, most notably in therapy-related myeloid neoplasms. However, the function of PPM1D in hematopoiesis and its contribution to tumor cell growth remain incompletely understood. Using conditional mouse models, we uncover a central role for Ppm1d in hematopoiesis and validate its potential as a therapeutic target. We find that Ppm1d regulates the competitive fitness and self-renewal of hematopoietic stem cells (HSCs) with and without exogenous genotoxic stresses. We also show that although Ppm1d activation confers cellular resistance to cytotoxic therapy, it does so to a lesser degree than p53 loss, informing the clonal competition phenotypes often observed in human studies. Notably, loss of Ppm1d sensitizes leukemias to cytotoxic therapies in vitro and in vivo, even in the absence of a Ppm1d mutation. Vulnerability to PPM1D inhibition is observed across many cancer types and dependent on p53 activity. Importantly, organism-wide loss of Ppm1d in adult mice is well tolerated, supporting the tolerability of pharmacologically targeting PPM1D. Our data link PPM1D gain-of-function mutations to the clonal expansion of HSCs, inform human genetic observations, and support the therapeutic targeting of PPM1D in cancer.

A metal-to-metal charge transfer induced green-yellow phosphor CsAlGe2O6:Bi3+ for full-spectrum LED devices.

With the development of solid-state lighting, full-spectrum lighting has gradually received extensive attention. Until now, Bi3+-doped narrow-band blue phosphors have been widely reported, but broadband green-yellow Bi3+-doped luminescent materials generated by metal-to-metal charge transfer have been rarely reported. In this study, a Bi3+ ion doped germanate luminescent material CsAlGe2O6:x%Bi3+ (1 ≤ x ≤ 11) is synthesized by a high-temperature sintering method. The phosphor can generate a broad green-yellow band peaking at 535 nm with a full width at half maximum of 165 nm under ultraviolet radiation. Through the analysis of the coordination environment, photoluminescence spectra and decay curves, the broadband emission spectra of Bi3+ ions are proved to be generated by the metal-to-metal charge transfer state and the 3P1 → 1S0 transition. By using theoretical research, luminescence kinetics, and Gaussian fitting, the luminescence mechanism of Bi3+ is examined. Meanwhile, the high quantum efficiency and superior thermal stability prove that the phosphor can be used as an efficient luminescent material in the field of full-spectrum LED devices.

Iron Nanoparticles Protected by Chainmail-structured Graphene for Durable Electrocatalytic Nitrate Reduction to Nitrogen.

The electrochemical nitrate reduction reaction (NO3 RR) is an appealing technology for regulating the nitrogen cycle. Metallic iron is one of the well-known electrocatalysts for NO3 RR, but it suffers from poor durability due to leaching and oxidation of iron during the electrocatalytic process. In this work, a graphene-nanochainmail-protected iron nanoparticle (Fe@Gnc) electrocatalyst is reported. It displays superior nitrate removal efficiency and high nitrogen selectivity. Notably, the catalyst delivers exceptional stability and durability, with the nitrate removal rate and nitrogen selectivity remained ≈96 % of that of the first time after up to 40 cycles (24 h for one cycle). As expected, the conductive graphene nanochainmail provides robust protection for the internal iron active sites, allowing Fe@Gnc to maintain its long-lasting electrochemical nitrate catalytic activity. This research proposes a workable solution for the scientific challenge of poor lasting ability of iron-based electrocatalysts in large-scale industrialization.

A novel efficient red-emitting K7SrY2B15O30: Eu3+ phosphor with non-concentration quenching and robust thermal stability for white LEDs.

Inhibiting energy migration between Eu3+ ions in a fixed host to get higher doping concentration is a permanent topic. Herein, a novel non-concentration quenching red-emitting K7SrY2-2xB15O30: xEu3+ (0.1 ≤ x ≤ 1.0) phosphor was synthesized via high-temperature sintering method. XRD measurement, Rietveld refinement results, and radius percentage deviation calculation demonstrated the phase purity and the occupation preference of Eu3+ ions. With continuously increasing doping Eu3+ ions, the absence of concentration quenching could be explained by long distance between two Eu3+ (7.012 Å) and the K7SrEu2B15O30 could exhibit striking photoluminescence performance with the highest emission wavelength centered at 617 nm. Meanwhile, under the radiation of 393 nm, the high internal quantum efficiency ( âˆ¼ 78.71 %), excellent color purity ( âˆ¼ 88.32 %) and robust thermal stability whose emission intensity at 140 °C could still reach âˆ¼ 97.31 % could guarantee its potential application. When coating BaMgAl10O17: Eu2+, (Ba, Sr)2SiO4: Eu2+, and K7SrEu2B15O30 on a near-ultraviolet chip, the bright white light with a low correlated color temperature of 4211 K and CIE color coordinates of (0.3675, 0.3556) could be obtained. Taking the analytic results above, the non-concentration quenching K7SrY2B15O30: Eu3+ compound has great potential to act as a candidate for red-emitting phosphors in solid-state lighting field.

Iron-Based Nanocatalysts for Electrochemical Nitrate Reduction.

Nitrate has a high level of stability and persistence in water, endangering human health and aquatic ecosystems. Due to its high reliability and efficiency, the electrochemical nitrate reduction reaction (NO3 RR) is regarded as the best available option for mitigating excess nitrate in water and wastewater, especially for the removal of trace levels of nitrate. One of the most critical factors in the electrochemical reduction are the catalysts, which directly affect the reaction efficiency of nitrate removal. Iron-based nanocatalysts, which have the advantages of nontoxicity, wide availability, and low cost, have emerged as a promising electrochemical NO3 RR material in recent years. This review covers major aspects of iron-based nanocatalysts for electrochemical NO3 RR, including synthetic methods, structural design, performance enhancement, electrocatalytic nitrate reduction test, and reduction mechanism. The recent progress of iron-based nanocatalysts for electrochemical NO3 RR and the mechanism of functional advantages for modified structures are reviewed from the perspectives of loading, doping, and assembly strategies, in order to realize the conversion from pollutant nitrate to harmless nitrogen or ammonia and other sustainable products. Finally, challenges and future directions for the development of low-cost and highly-efficient iron-based nanocatalysts are explored.

Synthetic libraries of immune cells displaying a diverse repertoire of chimaeric antigen receptors as a potent cancer immunotherapy.

Cancer immunotherapies rely on one or few specific tumour-associated antigens. However, the adaptive immune system relies on a large and diverse repertoire of antibodies for antigen recognition. Here we report the development and applicability of libraries of immune cells displaying diverse repertoires of chimaeric antigen receptors (CARs) that can recognize non-self antigens and display antigen-dependent clonal expansion, with the expanded population of tumour-specific effector cells leading to long-lasting antitumour responses in mouse models of epithelial tumours. The intravenous injection of synthetic libraries of murine CARs on TET2- T cells led to robust immunological memory and the recognition of mutated or evolved tumours, owing to the maintenance of CAR diversity. Off-the-shelf libraries of 106 murine or human CAR clones displayed on genetically modified human NK-92 cancer cells completely eliminated established tumours in mice with murine xenografts and patient-derived xenografts. Synthetically generated CAR libraries may aid the discovery of new CARs and the development of immunotherapies.

Bioaccessibility and movement of phenolic compounds from tomato (Solanum lycopersicum) during in vitro gastrointestinal digestion and colonic fermentation.

Tomatoes (Solanum lycopersicum) are highly involved in diets consumed worldwide, and are rich in bioactive compounds including phenolics, carotenoids and vitamins. In this study, four different varieties of fresh tomato pulp (Oxheart, Green Zebra, Kumato and Roma) were used to estimate the bioaccessibility of target phenolic compounds during in vitro gastrointestinal digestion and colonic fermentation, and to determine their antioxidant capacity. The production of short chain fatty acids (SCFAs) was also estimated during colonic fermentation. Among these, Roma displayed relatively higher total phenolic content (TPC) and free radical scavenging (2,2'-diphenyl-1-picrylhydrazyl (DPPH) assay) values after gastrointestinal digestion of 0.31 mg gallic acid equivalents (GAE) per g and 0.12 mg Trolox equivalents (TE) per g. Kumato exhibited the highest total flavonoid content (TFC) of 2.47 mg quercetin equivalents (QE) per g after 8 hours of colonic fermentation. Oxheart and Roma showed similar ferric reducing antioxidant power (FRAP) values of around 4.30 mg QE per g after 4 hours of faecal reaction. Catechin was the most bioaccessible phenolic compound in all fresh tomatoes, and could be completely decomposed after intestinal digestion, whereas the release of some bonded phenolic compounds required the action of gut microflora. Kumato and Green Zebra showed higher production of individual and total SCFAs for 16 hours of fermentation, which would provide more gut health benefits.

Generation and functional characterization of CAR exosomes.

Chimeric antigen receptor (CAR) T cells have attracted substantial attention in recent years as an emerging therapy for hematological and non-hematological malignancies. Despite the rapid and robust clinical responses, unexpected toxicity, such as cytokine release syndrome, still remains a major concern in this therapy. Moreover, the intrinsic ability of tumors to evade immune responses could lead to treatment failure especially in patients with solid tumors. These obstacles together highlight a need to improve current CAR-T therapy. Exosomes are small extracellular vesicles secreted by almost all cell types and have the capability of trafficking cargos to mediate many physiological/pathophysiological processes. Therefore, researchers have been trying to utilize exosomes as highly effective carriers to deliver various therapeutic agents to target cells. We reported that CAR-T cells release extracellular vesicles with the stimulation of antigens, mostly in the form of exosomes that carry CARs on their surface. These CAR exosomes express a high level of cytotoxic molecules and therefore inhibit tumor growth in an antigen-specific manner. Besides, CAR exosomes do not express programmed cell death protein 1 (PD1), and thus could circumvent the immunosuppressive mechanism caused by tumor cells. More importantly, the administration of CAR exosomes exhibited lower risk compared with CAR-T therapy in a preclinical in vivo model of cytokine release syndrome. All these advantages of CAR exosomes suggest that they may be promising therapeutic agents against tumors. Here, we describe the methods to generate CAR exosomes and the functional characterization of these therapeutic nano-vesicles.

Therapeutic antibodies under development for SARS-CoV-2.

The world is experiencing one of the most difficult moments in history with COVID-19, which has rapidly developed into a worldwide pandemic with a significant health and economic burden. Efforts to fight the virus, including prevention and treatment, have never stopped. However, no specific drugs or treatments have yet been found. Antibody drugs have never been absent in epidemics such as SARS, MERS, HIV, Ebola, and so on in the past two decades. At present, while research on the SARS-CoV-2 vaccine is in full swing, antibody drugs are also receiving widespread attention. Several antibody drugs have successfully entered clinical trials and achieved impressive therapeutic effects. Here, we summarize the therapeutic antibodies against SARS-CoV-2, as well as the research using ACE2 recombinant protein or ACE2-Ig fusion protein.

Advances in Drugs Targeting Lymphangiogenesis for Preventing Tumor Progression and Metastasis.

Metastasis of cancer cells from the primary tumor to other organs and tissues in the body is the leading cause of death in patients with malignancies. One of the principal ways cancer cells travel is through lymphatic vessels, and tumor invasion into the regional lymph nodes is a hallmark of early metastasis; thus, the formation of especially peritumoral lymphatic vessels is essential for tumor transportation that gives rise to further progression. In the past few decades, tumor-induced lymphangiogenesis has been testified to its tight correlation with lymphatic metastasis and poor clinical outcomes in multiple types of human malignancies, which warrants novel potential therapeutic targets for cancer treatment. As the understanding of underlying molecular mechanisms has grown tremendously over the years, an inexorable march of anti-lymphangiogenic therapy also aroused terrific interest. As a result, a great number of drugs have entered clinical trials, and some of them exhibited predominant contributions in cancer management. Herein, this review provides an updated summary of the current advances in therapies preventing lymphatic metastasis and discusses the validity of different applications.

CAR exosomes derived from effector CAR-T cells have potent antitumour effects and low toxicity.

Genetically engineered T cells expressing a chimeric antigen receptor (CAR) are rapidly emerging a promising new treatment for haematological and non-haematological malignancies. CAR-T therapy can induce rapid and durable clinical responses but is associated with unique acute toxicities. Moreover, CAR-T cells are vulnerable to immunosuppressive mechanisms. Here, we report that CAR-T cells release extracellular vesicles, mostly in the form of exosomes that carry CAR on their surface. The CAR-containing exosomes express a high level of cytotoxic molecules and inhibit tumour growth. Compared with CAR-T cells, CAR exosomes do not express Programmed cell Death protein 1 (PD1), and their antitumour effect cannot be weakened by recombinant PD-L1 treatment. In a preclinical in vivo model of cytokine release syndrome, the administration of CAR exosomes is relatively safe compared with CAR-T therapy. This study supports the use of exosomes as biomimetic nanovesicles that may be useful in future therapeutic approaches against tumours.

Treatment of murine lupus with TIGIT-Ig.

The TIGIT (T cell immunoreceptor with Ig and ITIM domains) protein is a co-inhibitory receptor that has been reported to suppress autoreactive T and B cells to trigger immunological tolerance. We generated a new recombinant protein by connecting the extracellular domain of murine TIGIT to the Fc region of the mouse immunoglobulin IgG2a. The fusion protein was then characterized. The results suggested that among mice with lupus that were treated with the TIGIT-Ig fusion protein, the onset of proteinuria was delayed, serum concentrations of autoantibodies, such as antinuclear antibodies, were reduced without a decrease in the total IgG concentrations, and the survival rate was significantly increased compared to those of the controls. In conclusion, TIGIT-Ig administration showed promising results for both the prevention and treatment of autoimmune diseases in mice. This indicates that treatment with recombinant human TIGIT-Ig shows promise as an effective way to treat human autoimmune diseases.

Targeting RyR2 with a phosphorylation site-specific nanobody reverses dysfunction of failing cardiomyocytes in rats.

Chronic PKA phosphorylation of ryanodine receptor 2 (RyR2) has been shown to increase diastolic sarcoplasmic reticulum (SR) Ca2+ leakage and lead to cardiac dysfunction. We hypothesize that intracellular gene delivery of an RyR2-targeting phosphorylation site-specific nanobody could preserve the contractility of the failing myocardium. In the present study, we acquired RyR2-specific nanobodies from a phage display library that were variable domains of Camelidae heavy chain-only antibodies. One of the nanobodies, AR185, inhibited RyR2 phosphorylation in vitro and was chosen for further investigation. We investigated the potential of adeno-associated virus (AAV)9-mediated cardiac expression of AR185 to combat postischemic heart failure (HF). AAV gene delivery elevated the intracellular expression of the AR185 protein in a rat model of ischemic HF, and this treatment normalized the systolic and diastolic dysfunction of the failing myocardium in vivo by reversing myocardial Ca2+ handling. Furthermore, AR185 gene transfer to failing cardiomyocytes reduced the frequency of SR calcium leaks, thereby restoring the attenuated intracellular calcium transients and SR calcium load. Moreover, AR185 gene transfer inhibited the PKA-mediated phosphorylation of RyR2 in failing cardiomyocytes. Our results provide preclinical experimental evidence that the cardiac expression of RyR2 nanobodies with AAV9 vectors is a promising therapeutic strategy for HF.-Li, T., Shen, Y., Lin, F., Fu, W., Liu, S., Wang, C., Liang, J., Fan, X., Ye, X., Tang, Y., Ding, M., Yang, Y., Lei, C., Hu, S. Targeting RyR2 with a phosphorylation site-specific nanobody reverses dysfunction of failing cardiomyocytes in rats.

Deferral of Consent in Acute Stroke Trials.

Background and Purpose- The ESCAPE trial (The Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion With Emphasis on Minimizing CT to Recanalization Times) was a multicentre, randomized controlled trial of endovascular thrombectomy versus standard care for patients with acute ischemic stroke that allowed patients to be enrolled with deferred consent. We investigated the knowledge and opinions of these patients or their authorized third parties about the consent process. Methods- All patients (or their authorized third parties) enrolled with deferral of consent in ESCAPE were invited to complete a 12-question survey within the first 4 days of enrollment and again at 90 days. Questions investigated knowledge of the ESCAPE trial and opinions on deferral of consent. Results- Of 56 patients enrolled with deferred consent, 33 (59%) completed the initial survey, and of these, 27 (81%) completed the 90-day follow-up. Enrollment with deferred consent was not associated with a significant difference in door-to-randomization times (50.5 versus 57 minutes; P=0.29) but allowed these 56 patients to participate in the trial. Only 52% of respondents understood that patients could be randomized to thrombectomy or standard care, although most understood the other basic principles of the trial. At baseline and at 90 days, respondents disagreed or strongly disagreed with deferred consent in acute stroke trials generally (82% and 78%) and in the ESCAPE trial specifically (93% and 91%). Conclusions- Respondents generally disagreed with the use of deferred consent for enrollment in the ESCAPE trial and in stroke trials more generally.

Synaptotagmin 1 and Ca2+ drive trans SNARE zippering.

Synaptotagmin 1 (Syt1) is a major Ca(2+)-sensor that evokes neurotransmitter release. Here we used site-specific fluorescence resonance energy transfer (FRET) assay to investigate the effects of Syt1 on SNAREpin assembly. C2AB, a soluble version of Syt1, had virtually no stimulatory effect on the rate of the FRET at N-terminus of SNARE complex both with and without Ca(2+), indicating C2AB does not interfere with the initial nucleation of SNARE assembly. However, C2AB-Ca(2+) accelerated the FRET rate significantly at membrane proximal region, indicating C2AB-Ca(2+) promotes the transition from a partially assembled SNARE complex to the fusion-competent SNAREpin. Similar enhancement was also observed at the end of the transmembrane domain of SNARE proteins. The stimulatory effect disappeared if there was no membrane or only neutral membrane present.