Gamma-aminobutyric acid as a regulator of astaxanthin production in Haematococcus lacustris under salinity: Exploring physiology, signaling, autophagy, and multi-omics landscape.

Haematococcus lacustris-derived natural astaxanthin has significant commercial value, but stressful conditions alone impair cell growth and reduce the total productivity of astaxanthin in industrial settings. This study used gamma-aminobutyric acid (GABA) to increase biomass, astaxanthin productivity, and tolerance to salinity. GABA under NaCl stress enhanced the biomass to 1.76 g/L, astaxanthin content to 30.37 mg g-1, and productivity to 4.10 mg/L d-1, outperforming the control. Further analysis showed GABA enhanced nitrogen assimilation, Ca2+ level, and cellular GABA content, boosting substrate synthesis, energy metabolism, osmoregulation, autophagy, and antioxidant defenses. GABA also activated signaling pathways involving phytohormones, cAMP, cGMP, and MAPK, aiding astaxanthin synthesis. The application of biomarkers (ethylene, salicylic acid, trans-zeatin) and an autophagy inhibitor cooperated with GABA to further enhance the total astaxanthin productivity under NaCl stress. Combining GABA with 25 µM salicylic acid maximized astaxanthin yield at 4.79 mg/L d-1, offering new strategies for industrial astaxanthin production.

Exploring the Lagged Correlation Between Baidu Index and Influenza-Like Illness - China, 2014-2019.

Introduction: This study investigated the lagged correlation between Baidu Index for influenza-related keywords and influenza-like illness percentage (ILI%) across regions in China. The aim is to establish a scientific foundation for utilizing Baidu Index as an early warning tool for influenza-like illness epidemics. Methods: In this study, data on ILI% and Baidu Index were collected from 30 provincial-level administrative divisions (PLADs) spanning April 2014 to March 2019. The Baidu Index was categorized into Overall Index, Ordinary Index, Prevention Index, Symptom Index, and Treatment Index based on search query themes. The lagged correlation between the Baidu Index and ILI% was examined through the cross-correlation function (CCF) method. Results: Correlating the Baidu Overall Index of 30 PLADs with ILI% revealed CCF values ranging from 0.46 to 0.86, with a median lag of 0.5 days. Subcategory analysis indicated that the Prevention Index and Symptom Index exhibited quicker responses to ILI%, with median lags of -9 and -0.5 days, respectively, compared to 0 and 3 days for the Ordinary and Treatment Indexes. The median lag days between the Baidu Index and the ILI% were earlier in the northern PLADs compared to the southern PLADs. Discussion: The Prevention and Symptom Indexes show promising predictive capabilities for influenza-like illness epidemics.

Comparison Between Threshold Method and Artificial Intelligence Approaches for Early Warning of Respiratory Infectious Diseases - Weifang City, Shandong Province, China, 2020-2023.

Introduction: Respiratory infectious diseases, such as influenza and coronavirus disease 2019 (COVID-19), present significant global public health challenges. The emergence of artificial intelligence (AI) and big data offers opportunities to improve traditional disease surveillance and early warning systems. Methods: The study analyzed data from January 2020 to May 2023, comprising influenza-like illness (ILI) statistics, Baidu index, and clinical data from Weifang. Three methodologies were evaluated: the adaptive dynamic threshold method (ADTM) for dynamic threshold adjustments, the machine learning supervised method (MLSM), and the machine learning unsupervised method (MLUM) utilizing anomaly detection. The comparison focused on sensitivity, specificity, timeliness, and warning consistency. Results: ADTM issued 37 warnings with a sensitivity of 71% and a specificity of 85%. MLSM generated 35 warnings, with a sensitivity of 82% and a specificity of 87%. MLUM produced 63 warnings with a sensitivity of 100% and specificity of 80%. The initial warnings from ADTM and MLUM preceded those from MLSM by five days. The Kappa coefficient indicated moderate agreement between the methods, with values ranging from 0.52 to 0.62 (P<0.05). Discussion: The study explores the comparison between traditional methods and two machine learning approaches for early warning systems. It emphasizes the validation of machine learning's reliability and underscores the unique advantages of each method. Furthermore, it stresses the significance of integrating machine learning models with various data sources to enhance public health preparedness and response, alongside acknowledging limitations and the need for broader validation.

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.

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.

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.

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.