Efficacy, safety, and immunogenicity of SARS-CoV-2 mRNA vaccine (Omicron BA.5) LVRNA012: a randomized, double-blind, placebo-controlled phase 3 trial.

Background: We aimed to evaluate the efficacy, safety, and immunogenicity of a SARS-CoV-2 mRNA vaccine (Omicron BA.5) LVRNA012 given as the booster in immunized but SARS-CoV-2 infection-free adults in China. Methods: This is a single-center, randomized, double-blind, placebo-controlled phase 3 clinical trial enrolling healthy adult participants (≥18 years) who had completed two or three doses of inactivated COVID-19 vaccines at least 6 months before, in Bengbu, Anhui province, China. Eligible participants were randomly assigned (1:1) to receive a booster intramuscular vaccination with an LVRNA012 vaccine (100ug) or placebo. The primary endpoint was the protective efficacy of a booster dose of the LVRNA012 vaccine or placebo against symptomatic COVID-19 of any severity 14 days after vaccination. Laboratory-confirmed COVID-19 infections were identified from 14 days to 180 days after intervention, with active surveillance for symptomatic illness 8 times per month between 7 to 90 days and at least once per month between 90 to 180 days after intervention. Results: 2615 participants were recruited and randomly assigned in a 1:1 ratio to either the vaccine group (1308) or the placebo group (1307). A total of 141 individuals (46 in the LVRNA012 group and 95 in the placebo group) developed symptomatic COVID-19 infection 14 days after the booster immunization, showing a vaccine efficacy of 51.9% (95% CI, 31.3% to 66.4%). Most infections were detected 90 days after intervention during a period when XBB was prevalent in the community. Adverse reactions were reported by 64% of participants after the LVRNA012 vaccination, but most of them were mild or moderate. The booster vaccination with the LVRNA012 mRNA vaccine could significantly enhance neutralizing antibody titers against the Omicron variant XBB.1.5 (GMT 132.3 [99.8, 175.4]) than did those in the placebo group (GMT 12.5 [8.4, 18.7]) at day 14 for the previously immunized individuals. Conclusion: The LVRNA012 mRNA vaccine is immunogenic, and shows robust efficacy in preventing COVID-19 during the omicron-predominate period. Clinical trial registration: ClinicalTrials.gov, identifier NCT05745545.

Probiotics Armed with In Situ Mineralized Nanocatalysts and Targeted Biocoatings for Multipronged Treatment of Inflammatory Bowel Disease.

While oral probiotics show promise in treating inflammatory bowel disease, the primary challenge lies in sustaining their activity and retention within the inflamed gastrointestinal environment. In this work, we develop an engineered probiotic platform that is armed with biocatalytic and inflamed colon-targeting nanocoatings for multipronged management of IBD. Notably, we achieve the in situ growth of artificial nanocatalysts on probiotics through a bioinspired mineralization strategy. The resulting ferrihydrite nanostructures anchored on bacteria exhibit robust catalase-like activity across a broad pH range, effectively scavenging ROS to alleviate inflammation. The further envelopment with fucoidan-based shields confers probiotics with additional inflamed colon-targeting functions. Upon oral administration, the engineered probiotics display markedly improved viability and colonization within the inflamed intestine, and they further elicit boosted prophylactic and therapeutic efficacy against colitis through the synergistic interplay of nanocatalysis-based immunomodulation and probiotics-mediated microbiota reshaping. The robust and multifunctional probiotic platforms offer great potential for the comprehensive management of gastrointestinal disorders.

Macrophages-Based Biohybrid Microrobots for Breast Cancer Photothermal Immunotherapy by Inducing Pyroptosis.

Pyroptosis-based immunotherapy can escape drug resistance as well as inhibit metastasis. It is urgently required to develop a delivery platform to induce targeted tumor-specific pyroptosis for cancer immunotherapy. Herein, macrophages-based biohybrid microrobots (IDN@MC) are constructed with IR-macrophage and decitabine-loaded Metal-organic frameworks (DZNPs). The integration of fluorescence photosensitizers and pH-sensitive DZNPs endow the microrobots properties such as photothermal conversion, fluorescent navigation, targeted drug delivery, and controlled drug release. In light of the inherent tumor targeting, tumor accumulation of IDN@MC is facilitated. Due to the sustained release of decitabine from packaged DZNPs, the host macrophages are differentiated into M1 phenotypes to exert the tumor phagocytosis at the tumor site, directly transporting the therapeutic agents into cancer cells. With laser control, the rapid and durable caspase 3-cleaved gasdermin E (GSDME)-related tumor pyroptosis is achieved with combined photothermal-chemotherapy, releasing inflammatory factors such as lactate dehydrogenase and interleukin-18. Subsequently, the robust and adaptive immune response is primed with dendritic cell maturation to initiate T-cell clone expansion and modulation of the immune suppressive microenvironment, thus enhancing the tumor immunotherapy to inhibit tumor proliferation and metastasis. This macrophages-based biohybrid microrobot is an efficient strategy for breast cancer treatment to trigger photo-induced pyroptosis and augment the immune response.

Melatonin, a phytohormone for enhancing the accumulation of high-value metabolites and stress tolerance in microalgae: Applications, mechanisms, and challenges.

High-value metabolites, such as carotenoids, lipids, and proteins, are synthesized by microalgae and find applications in various fields, including food, health supplements, and cosmetics. However, the potential of the microalgal industry to serve these sectors is constrained by low productivity and high energy consumption. Environmental stressors can not only stimulate the accumulation of secondary metabolites in microalgae but also induce oxidative stress, suppressing cell growth and activity, thereby resulting in a decrease in overall productivity. Using melatonin (MT) under stressful conditions is an effective approach to enhance the productivity of microalgal metabolites. This review underscores the role of MT in promoting the accumulation of high-value metabolites and enhancing stress resistance in microalgae under stressful and wastewater conditions. It discusses the underlying mechanisms whereby MT enhances metabolite synthesis and improves stress resistance. The review also offers new perspectives on utilizing MT to improve microalgal productivity and stress resistance in challenging environments.

Characteristics of Amorphophallus konjac as indicated by its genome.

Amorphophallus konjac, belonging to the genus Amorphophallus of the Araceae family, is an economically important crop widely used in health products and biomaterials. In the present work, we performed the whole-genome assembly of A. konjac based on the NovaSeq platform sequence data. The final genome assembly was 4.58 Gb with a scaffold N50 of 3212 bp. The genome includes 39,421 protein-coding genes, and 71.75% of the assemblies were repetitive sequences. Comparative genomic analysis showed 1647 gene families have expanded and 2685 contracted in the A. konjac genome. Likewise, genome evolution analysis indicated that A. konjac underwent whole-genome duplication, possibly contributing to the expansion of certain gene families. Furthermore, we identified many candidate genes involved in the tuber formation and development, cellulose and lignification synthesis. The genome of A. konjac obtained in this work provides a valuable resource for the further study of the genetics, genomics, and breeding of this economically important crop, as well as for evolutionary studies of Araceae family.

Phase I study of a non-S2P SARS-CoV-2 mRNA vaccine LVRNA009 in Chinese adults.

BACKGROUND: COVID-19 caused by SARS-CoV-2 is a great threat to public health. We present the safety and immunogenicity data from a phase I trial in China of an mRNA vaccine (LVRNA009). METHODS: In the single-centre, double-blind, placebo-controlled and dose-escalation study, 72 healthy unvaccinated adults aged 18-59 years were randomized (3:1) to receive LVRNA009 with one of three vaccine dosage (25, 50 and 100 µg) or placebo, to evaluate for the safety, tolerability and immunogenicity of LVRNA009. RESULTS: All these participants received two injections 28 days apart. No adverse events higher than grade 2 were reported during the study. A total of 30 participants (42 %) reported solicited adverse reactions during the first 14 days after vaccinations. Of the events reported, fever (n = 11, 15 %) was the most common systemic adverse reaction, and pain at the injection site (n = 17, 24 %) was the most frequent solicited local adverse reaction. Anti-S-protein IgG and neutralising antibodies were observed to have been induced 14 days after the first dose, significantly increased 7 days after the second dose, and remained at a high level 28 days after the second dose. Specific T-cell responses peaked 7 days and persisted 28 days after second vaccination. CONCLUSION: LVRNA009 has demonstrated promising results in safety and tolerability at all three dose levels among Chinese adults. LVRNA009 at three dose levels could rapidly induce strong humoral and cellular immune responses, including binding and neutralising antibody production and IFN- γ secretion, which showed good immunogenicity. CLINICAL TRIAL REGISTRATION NUMBER: Clinicaltrials.gov NCT05364047; Chictr.org.cn ChiCTR2100049349.

Comprehensive understanding of the regulatory mechanism by which selenium nanoparticles boost CO2 fixation and cadmium tolerance in lipid-producing green algae under recycled medium.

Recycled medium plus cadmium is a promising technique for reducing the cultivation cost and enhancing the yield of microalgae lipids. However, oxidative stress and cadmium toxicity significantly hinder the resulting photosynthetic efficiency, cell growth and cell activity. Herein, selenium nanoparticles (SeNPs) were used to increase the total biomass, biolipid productivity, and tolerance to cadmium. Wide-ranging analyses of photosynthesis, energy yield, fatty acid profiles, cellular ultrastructure, and oxidative stress biomarkers were conducted to examine the function of SeNPs in CO2 fixation and cadmium resistance in Ankistrodesmus sp. EHY. The application of 15 µM cadmium and 2 mg L-1 SeNPs further enhanced the algal biomass productivity and lipid productivity to 500.64 mg L-1 d-1 and 301.14 mg L-1 d-1, respectively. Moreover, the rates of CO2 fixation, chlorophyll synthesis and total nitrogen removal were similarly increased by the application of SeNPs. Exogenous SeNPs strengthened cell growth and cadmium tolerance by upregulating photosynthesis, the TCA cycle and the antioxidant system, reducing the uptake and translocation of cadmium, and decreasing the levels of reactive oxidative stress (ROS), extracellular polymeric substances (EPSs) and cellular Cd2+ level in EHY under recycled medium and cadmium stress conditions. Additionally, a maximum energy yield of 127.40 KJ L-1 and a lipid content of 60.15% were achieved in the presence of both SeNPs and cadmium stress. This study may inspire the efficient disposal of recycled medium and biolipid production while also filling the knowledge gaps regarding the mechanisms of SeNP functions in carbon fixation and cadmium tolerance in microalgae.

Neutrophil Camouflaged Stealth Nanovehicle for Photothermal-Induced Tumor Immunotherapy by Triggering Pyroptosis.

The regulation of tumor immunosuppressive microenvironments via precise drug delivery is a promising strategy for preventing tumor recurrence and metastasis. Inspired by the stealth strategy, a stealthy nanovehicle based on neutrophil camouflage is developed to achieve precise delivery and tumor immunotherapy by triggering pyroptosis. The nanovehicle comprises anti-CD11b- and IR820-conjugated bovine serum albumin nanoparticles loaded with decitabine. Camouflaged by neutrophils, the nanovehicles achieve efficient tumor delivery by neutrophil hitchhiking owing to the biotropism of neutrophils for tumors. The fluorescent signal molecule, IR820, on the nanovehicle acts as a navigation monitor to track the precise delivery of the nanovehicle. The released decitabine upregulates gasdermin E, and laser irradiation activates caspase-3, thereby resulting in pyroptosis, which improves the system's adaptive immune response. In a triple-negative breast cancer animal model, it regulates the immunosuppressive microenvironment for effective tumor immunotherapy and induces a long-lasting and strong immune memory to prevent lung metastasis.

Exogenous prolinebooststheco-accumulation ofastaxanthin and biomassin stress-induced Haematococcus pluvialis.

This paper aims to explore the role of proline (Pro) in the production of biomass and astaxanthin (AST) in stress-induced Haematococcus pluvialis. The astaxanthin content and productivity were 24.02 mg g-1 and 2.22 mg/L d-1 under abiotic stresses, respectively. After 100 µM Pro supplementation, the biomass, AST and lipid contents reached 1.43 g/L, 29.91 mg g-1 and 56.79 %, which were enhanced by 19.16 %, 33.52 % and 11.08 %, respectively, compared to the control. Pro-treated regulated chlorophyll, carbohydrate and protein accumulation and upregulated carotenogenic, lipogenic and antioxidant enzymes-associated gene levels; as well as increased endogenous Pro content, but reduced ROS (Reactive oxygen species) and MDA (Malondialdehyde) levels and alleviated oxidative stress, which might be involved in AST biosynthesis. Further data showed Pro has a positive role in biomass and AST coaccumulation in different H. pluvialis species, suggesting application of Pro was an effective strategy to improve AST productivity of H. pluvialis.

A low-cost technique for biodiesel production in Ankistrodesmus sp. EHY by using harvested microalgal effluent.

The present study aims to use Ankistrodesmus sp. EHY to develop a viable and economic lipid production strategy using recycling of harvested microalgal effluent. In comparison to the control, the highest lipid content (52.4 %) and productivity (250.72 mg L-1 d-1) were achieved when 40 % recycled medium was used. Consistent with the trend of lipid accumulation, the six key lipogenetic genes were upregulated, as well as reactive oxygen species (ROS), glutathione (GSH) and genes encoding antioxidant enzymes during cultivation in recycled medium. Moreover, the consumption of dissolved organic carbon (DOC) and the increased humic acid (HA) in the recycled medium might also be associated with lipid biosynthesis. The biodiesel parameters of alga biomass-derived lipids were fitted to the standard of commercial biodiesel. In conclusion, this study offers an economically viable strategy for microalgal biofuel production and wastewater treatment using recycling of harvested microalgal effluent.

Myo-inositol facilitates astaxanthin and lipid coproduction in Haematococcus pluvialis by regulating oxidative stress and ethylene signalling.

In the present study, exogenous myo-inositol (MI) was applied to induce natural astaxanthin and biolipid accumulation in Haematococcus pluvialis. Under 200 µM MI, algal cells exhibited 62.11 % and 34.67 % increases in astaxanthin and lipid content, respectively, compared to the control. The carotenogenesis and lipogenesis genes were upregulated by induction of MI. Interestingly, MI addition elevated the ethylene (ETH) content and activated antioxidant enzyme-associated gene levels, which could be involved in alleviating oxidative stress. Further data showed that the ETH signal played a positive function in stimulating astaxanthin biosynthesis under MI induction. Supplementation with ethephon plus MI boosted the astaxanthin content to 33.08 ± 0.03 mg g-1 by further upregulating astaxanthin biosynthesis genes and blocking reactive oxidative species (ROS) levels, and vice versa under ETH inhibition. This study provides a potential induction approach for natural astaxanthin production and explains the role of ethylene signalling in regulating astaxanthin synthesis by H. pluvialis.

Hydrogel/nanoparticles-mediated cooperative combination of antiangiogenesis and immunotherapy.

Vascular abnormalities are directly related to the tumor immunosuppressive microenvironment, which is an important obstacle to effective immunotherapy. The combination of antiangiogenesis therapy and immunotherapy may promote a mutually reinforcing cycle of immune reprogramming and vascular normalization to increase the effectiveness of immunotherapy. Herein, a hydrogel/nanosystem-mediated antiangiogenesis combined immunotherapy strategy was used to regulate the tumor microenvironment by the controlled release of apatinib, CD47 antibody (aCD47), and CpG. The combination of hydrogel with nanoparticles protected drug activity and maintained a long-term slow release of the drug for maximum synergistic efficacy. Apatinib promotes vascular normalization in tumors and enhances the efficacy of aCD47-based immunotherapy. The addition of immunoadjuvant CpG further enhanced antigen presentation and stimulated the anti-tumor activity of macrophages to strengthen the efficacy of antiangiogenesis combined immunotherapy. The main effector immune cells, including CD4+ T, CD8+ T, NK, and activity DCs, were significantly increased after combination treatment, while the proportion of various immunosuppressive cells decreased significantly, especially MDSCs and M2-polarized macrophages. Based on an effective systemic immune response, the hydrogel/nanoparticle-mediated cooperative combination of antiangiogenesis and immunotherapy enhanced the synergistic effect for primary tumors and prevented metastasis for tumor treatment. The biomaterial-mediated antiangiogenesis combined immunotherapy strategy is a promising strategy for effective immunotherapy. STATEMENT OF SIGNIFICANCE: Relieving immunosuppression of the tumor microenvironment is the key to restoring and rebuilding the normal anti-tumor immune defense of the body. Vascular abnormalities are directly related to the tumor immunosuppressive microenvironment, which is an important obstacle to effective immunotherapy. The combination of antiangiogenesis and immunotherapy may promote a mutually reinforcing cycle of immune reprogramming and vascular normalization to increase the effectiveness of immunotherapy. For the combination of antiangiogenesis and immunotherapy, effective drug delivery to overcome local immune tolerance and regulate the tumor microenvironment to increase therapeutic effects is an important issue. The hydrogel/nanomaterial composite system constructs a dual sustained-release system to achieve step-by-step controlled release of antiangiogenic drugs and immune immunotherapy drugs to promote cooperative combination therapy.

Promoting lutein production from the novel alga Acutodesmus sp. by melatonin induction.

In the current research, a novel microalgae strain was isolated from Yajiageng Red Rock Beach and identified as Acutodesmus sp. HLGY. To obtain high-efficiency production of lutein from algae, the feasibility of using melatonin (MT) to increase lutein yield of Acutodesmus sp. HLGY was evaluated. Under the 7.5 µM MT treatment, the lutein content and lutein productivity were 17.44 mg g-1 and 46.50 mg L-1 d-1, which were 1.53 times those of the control. Furthermore, exogenous MT increased the transcripts of key lutein synthesis- and antioxidant enzyme-related genes. Simultaneously, the carbohydrate, protein, and cellular reactive oxygen species (ROS) levels and lipid content were suppressed. More importantly, the ethylene and γ-aminobutyric acid contents were markedly increased by MT, which may be linked to the increase in lutein biosynthesis. This study proposes a valuable biotechnological approach for lutein production via a novel Acutodesmus sp. strain using MT induction and provides insights into the role of MT in promoting lutein biosynthesis.

Phytohormone-like small biomolecules for microalgal biotechnology.

Microalgae are highly adaptable to abiotic stress and produce valuable metabolites, but microalgal commercialization is still difficult because of minimal yields. The application of phytohormone-like small biomolecules is effective in simultaneously improving the productivity of valuable microalgal biomass-derived metabolites and stress tolerance. This represents a significant opportunity for microalgal biotechnology.

The associative induction of succinic acid and hydrogen sulfide for high-producing biomass, astaxanthin and lipids in Haematococcus pluvialis.

To obtain higher yield of natural astaxanthin, the present study aims to develop a viable and economic induction strategy for astaxanthin production comprising succinic acid (SA) combined with sodium hydrosulfide (NaHS). The biomass (1.33 g L-1), astaxanthin concentration (44.96 mg L-1), astaxanthin content (163.55 pg cell-1), and lipid content (55.34%) were achieved under 1.0 mM SA and 100 µM NaHS treatment. These results were concomitant with enhanced hydrogen sulfide (H2S) but diminished reactive oxide species (ROS). Further study discovered that endogenous H2S could improve astaxanthin and lipid coproduction under SA induction by mediating related gene transcript levels and ROS signalling. Additionally, the concentrations of biomass and astaxanthin increased to 2.14 g L-1 and 66.25 mg L-1, respectively, under the induction of SA and NaHS in a scaled-up bioreactor. Briefly, the work proposed a novel feasible strategy for high yields of biomass and astaxanthin by H. pluvialis.

Gamma-aminobutyric acid coupled with copper ion stress stimulates lipid production of green microalga Monoraphidium sp. QLY-1 through multiple mechanisms.

Induction of copper ion (Cu2+) stress is a method used to increase lipid accumulation in microalgae, but it decreases cell growth. In this work, the impacts of gamma-aminobutyric acid (GABA) coupled with Cu2+ stress on the biomass and oil yield in Monoraphidium sp. QLY-1 were investigated. Results suggested that the combined treatment of GABA and Cu2+ resulted in a higher lipid content (55.13%) than Cu2+ treatment (48.43%). Furthermore, GABA addition upregulated the levels of lipid-relevant genes, cellular GABA, ethylene (ETH), and antioxidant enzyme activities and alleviated oxidative damage caused by Cu2+ stress. The autophagy-relevant gene atg8 was also upregulated by GABA treatment. Further exploration indicated that cell autophagy induced the lipid content up to 58.09% with GABA and Cu2+ stress treatment. This investigation demonstrates that the coupling strategy can stimulate lipid production and shed light on the underlying mechanisms in lipid biosynthesis, cell autophagy, and stress response of microalgae.

Enhancing astaxanthin and lipid coproduction in Haematococcus pluvialis by the combined induction of plant growth regulators and multiple stresses.

Coupling chemical induction and abiotic stresses is a beneficial strategy for astaxanthin (Asta) induction in Haematococcus pluvialis. The combined application of melatonin (MT) and putrescine (Put) induced Asta and lipid biosynthesis in H. pluvialis under adverse conditions. Under MT and Put inductions, the highest Asta and lipid contents were 3.64% and 55.84%, which were 1.71- and 1.17-times higher than the control group, respectively. The combination of MT and Put also enhanced the expression of carotenogenic, lipogenic and antioxidant enzyme genes. Additionally, this combined treatment increased the endogenous Put content while decreasing the reactive oxygen species (ROS) and γ-aminobutyric acid (GABA) levels. Further results proved that endogenous Put promoted Asta production and alleviated oxidative stress by regulating carotenogenesis and GABA and ROS signaling. This study describes a potential process for stimulating Asta and lipid coproduction and highlights the connections among MT, Put, signaling molecules, Asta and lipid synthesis in H. pluvialis.

Sodium chloride stimulates the biomass and astaxanthin production by Haematococcus pluvialis via a two-stage cultivation strategy.

A major challenge facing by astaxanthin industrialization is the low productivity and high production costs. This study established a two-stage cultivation strategy based on the application of NaCl to improve the production of biomass and astaxanthin by Haematococcus pluvialis. During the first growth stage, 12.5 mg L-1 NaCl led to a remarkable enhancement in biomass, which was 1.28 times compared with the control. Moreover, 2 g L-1 NaCl stimulated the astaxanthin content from 12.18 mg g-1 to 25.92 mg g-1 during the second induction stage. Simultaneously, salinity stress application increased the lipids and GABA contents, as well as the levels of Ca2+ and carotenogenic genes' expression, but suppressed the contents of carbohydrate and protein and high-light induced-ROS. This study proposed a simple and convenient strategy for efficient coproduction of biomass and astaxanthin and provides insights into the underlying mechanism of astaxanthin biosynthesis in H. pluvialis induced by salinity stress.

Coupling of myo-inositol with salinity regulates ethylene-induced microalgal lipid hyperproduction in molasses wastewater.

With the goal of cost-effective and high-efficient microalgae-based biodiesel production, this study evaluated the feasibility of the joint strategy concerning myo-inositol (MI) and salinity stress on lipid productivity of Monoraphidium sp. QLY-1 in molasses wastewater (MW). The maximal lipid productivity (147.79 mg L-1 d-1) was obtained under combined 0.5 g L-1 MI and 10 g L-1 NaCl treatment, which was 1.40-fold higher than the control. Meanwhile, the nutrients removal from MW was markedly increased under MI-NaCl treatment. Moreover, exogenous MI upregulated key lipogenic genes' expressions, activated autophagic activity and ethylene (ET) signaling, and ultimately alleviated the salinity-induced damage via reactive oxygen species (ROS) signaling. Further pharmacologic experiment confirmed the indispensable role of ET in the lipogenesis progress under the combined treatment. These data demonstrated the combined salinity stress and MI treatment to be capable for lipid hyperproduction and wastewater nutrients removal, which contributes to practically integrating the microalgae cultivation with wastewater treatment.