Advances and prospects in microbial production of biotin.

Biotin, serving as a coenzyme in carboxylation reactions, is a vital nutrient crucial for the natural growth, development, and overall well-being of both humans and animals. Consequently, biotin is widely utilized in various industries, including feed, food, and pharmaceuticals. Despite its potential advantages, the chemical synthesis of biotin for commercial production encounters environmental and safety challenges. The burgeoning field of synthetic biology now allows for the creation of microbial cell factories producing bio-based products, offering a cost-effective alternative to chemical synthesis for biotin production. This review outlines the pathway and regulatory mechanism involved in biotin biosynthesis. Then, the strategies to enhance biotin production through both traditional chemical mutagenesis and advanced metabolic engineering are discussed. Finally, the article explores the limitations and future prospects of microbial biotin production. This comprehensive review not only discusses strategies for biotin enhancement but also provides in-depth insights into systematic metabolic engineering approaches aimed at boosting biotin production.

Enhancement of vitamin B6 production driven by omics analysis combined with fermentation optimization.

BACKGROUND: Microbial engineering aims to enhance the ability of bacteria to produce valuable products, including vitamin B6 for various applications. Numerous microorganisms naturally produce vitamin B6, yet the metabolic pathways involved are rigorously controlled. This regulation by the accumulation of vitamin B6 poses a challenge in constructing an efficient cell factory. RESULTS: In this study, we conducted transcriptome and metabolome analyses to investigate the effects of the accumulation of pyridoxine, which is the major commercial form of vitamin B6, on cellular processes in Escherichia coli. Our omics analysis revealed associations between pyridoxine and amino acids, as well as the tricarboxylic acid (TCA) cycle. Based on these findings, we identified potential targets for fermentation optimization, including succinate, amino acids, and the carbon-to-nitrogen (C/N) ratio. Through targeted modifications, we achieved pyridoxine titers of approximately 514 mg/L in shake flasks and 1.95 g/L in fed-batch fermentation. CONCLUSION: Our results provide insights into pyridoxine biosynthesis within the cellular metabolic network for the first time. Our comprehensive analysis revealed that the fermentation process resulted in a remarkable final yield of 1.95 g/L pyridoxine, the highest reported yield to date. This work lays a foundation for the green industrial production of vitamin B6 in the future.

Coordination cages integrated into swelling poly(ionic liquid)s for guest encapsulation and separation.

Coordination cages have been widely reported to bind a variety of guests, which are useful for chemical separation. Although the use of cages in the solid state benefits the recycling, the flexibility, dynamicity, and metal-ligand bond reversibility of solid-state cages are poor, preventing efficient guest encapsulation. Here we report a type of coordination cage-integrated solid materials that can be swelled into gel in water. The material is prepared through incorporation of an anionic FeII4L6 cage as the counterion of a cationic poly(ionic liquid) (MOC@PIL). The immobilized cages within MOC@PILs have been found to greatly affect the swelling ability of MOC@PILs and thus the mechanical properties. Importantly, upon swelling, the uptake of water provides an ideal microenvironment within the gels for the immobilized cages to dynamically move and flex that leads to excellent solution-level guest binding performances. This concept has enabled the use of MOC@PILs as efficient adsorbents for the removal of pollutants from water and for the purification of toluene and cyclohexane. Importantly, MOC@PILs can be regenerated through a deswelling strategy along with the recycling of the extracted guests.

Diverse nucleotide substitutions in rice base editing mediated by novel TadA variants.

CRISPR-mediated base editors have been widely used to correct defective alleles and create novel alleles by artificial evolution in rapid genetic improvement of crops. The editing capabilities of base editors strictly rely on the performance of various nucleotide modification enzymes. Compared to the well-developed adenine base editors (ABEs), cytosine base editors (CBEs) and dual base editors suffer from unstable editing efficiency and pattern at different genomic loci in rice, significantly limiting their application. Here, the activities of multiple evolved TadA8e variants in base editing have been comprehensively examined in rice. We found that both TadA-CDd and TadA-E27R/N46L achieve more robust C-to-T editing than previously reported hyperactive hAID*Δ, whereas TadA-CDd outperformed TadA-E27R/N46L. Also, the C-to-G base editor (CGBE) engineered with TadA-CDd and OsUNG performs highly efficient C-to-G editing in rice compared to TadA-N46P. In addition, the dual base editor, which was constructed with a single protein TadDE, enables simultaneously edit C-to-T and A-to-G at high efficiency in rice. Collectively, our study demonstrates that TadA8e derivatives improve both CBE and dual base editor in rice, provide a powerful way in inducing diverse nucleotide substitutions for plant genome editing.

Engineering and finetuning expression of SerC for balanced metabolic flux in vitamin B6 production.

Vitamin B6 plays a crucial role in cellular metabolism and stress response, making it an essential component for growth in all known organisms. However, achieving efficient biosynthesis of vitamin B6 faces the challenge of maintaining a balanced distribution of metabolic flux between growth and production. In this study, our focus is on addressing this challenge through the engineering of phosphoserine aminotransferase (SerC) to resolve its redundancy and promiscuity. The enzyme SerC was semi-designed and screened based on sequences and predicted kcat values, respectively. Mutants and heterologous proteins showing potential were then fine-tuned to optimize the production of vitamin B6. The resulting strain enhances the production of vitamin B6, indicating that different fluxes are distributed to the biosynthesis pathway of serine and vitamin B6. This study presents a promising strategy to address the challenge posed by multifunctional enzymes, with significant implications for enhancing biochemical production through engineering processes.

Recent Advances in the Crosstalk between Brassinosteroids and Environmental Stimuli.

Due to their sessile lifestyle, plants need to optimize their growth in order to adapt to ever-changing environments. Plants receive stimuli from the environment and convert them into cellular responses. Brassinosteroids (BRs), as growth-promoting steroid hormones, play a significant role in the tradeoff between growth and environmental responses. Here, we provide a comprehensive summary for understanding the crosstalk between BR and various environmental stresses, including water availability, temperature fluctuations, salinization, nutrient deficiencies and diseases. We also highlight the bottlenecks that need to be addressed in future studies. Ultimately, we suppose to improve plant environmental adaptability and crop yield by excavating natural BR mutants or modifying BR signaling and its targets.

Isoflurane pretreatment protects against myocardial ischemia/reperfusion injury via mediating lncRNA CASC15/miR-542-3p axis.

The protective effect of isoflurane on cardiomyocyte ischemia/reperfusion injury (I/RI) was explored in hypoxia and reoxygenation (H/R) induced cardiomyocyte injury model. In terms of mechanism, the participation of long non-coding RNA CASC15/microR-542-3p axis was further discussed. H9c2 cells received H/R treatment to mimic myocardial I/RI. RT-qPCR was performed to quantify mRNA levels. Cell viability and apoptosis were evaluated after isoflurane pretreatment and cell transfection. ELISA was performed to measure the concentrations of inflammatory/oxidative stress-related cytokines (TNF-α, IL-6, MDA, SOD). The target relationship between CASC12 and miR-542-3p was determined via dual-luciferase reporter assay. Isoflurane pretreatment alleviated H/R-induced cell viability suppression and cell apoptosis promotion, which was accompanied by CASC15 downregulation. CASC15 overexpression abolished the influence of isoflurane on cardiomyocytes' viability and apoptosis. H/R-induced excessive release of TNF-α and IL-6 was hold down by isoflurane, which was re-activated after CASC15 overexpression. The concentration changes of both MDA and SOD by isoflurane were reversed by CASC15 overexpression. CASC15 functioned as miR-542-3p sponger, and miR-542-3p overexpression attenuated the effect of isoflurane and CASC15 on H/R-induced cardiac I/RI. Isoflurane pretreatment was beneficial for the alleviation of cardiac I/RI by inhibiting oxidative stress and myocardial inflammatory response. CASC15/miR-542-3p axis was required for isoflurane to exhibit its protective activity against cardiac I/RI.

Catalyzing satellite communication: A 20W Ku-Band RF front-end power amplifier design and deployment.

This paper presents a groundbreaking Ku-band 20W RF front-end power amplifier (PA), designed to address numerous challenges encountered by satellite communication systems, including those pertaining to stability, linearity, cost, and size. The manuscript commences with an exhaustive discussion of system design and operational principles, emphasizing the intricacies of low-noise amplification, and incorporating key considerations such as noise factors, stability analysis, gain, and gain flatness. Subsequently, an in-depth study is conducted on various components of the RF chain, including the pre-amplification module, driver-amplification module, and final-stage amplification module. The holistic design extends to the inclusion of the display and control unit, featuring the power-control module, monitoring module, and overall layout design of the PA. It is meticulously tailored to meet the specific demands of satellite communication. Following this, a thorough exploration of electromagnetic simulation and measurement results ensues, providing validation for the precision and reliability of the proposed design. Finally, the feasibility of that design is substantiated through systematic system design, prototype production, and exhaustive experimental testing. It is noteworthy that, in the space-simulation environmental test, emphasis is placed on the excellent performance of the Star Ku-band PA within the 13.75GHz to 14.5GHz frequency range. Detailed power scan measurements reveal a P1dB of 43dBm, maintaining output power flatness < ± 0.5dBm across the entire frequency and temperature spectrum. Third-order intermodulation scan measurements indicate a third-order intermodulation of ≤ -23dBc. Detailed results of power monitoring demonstrate a range from +18dBm to +54dBm. Scans of spurious suppression and harmonic suppression, meanwhile, show that the PA evinces spurious suppression ≤ -65dBc and harmonic suppression ≤ -60dBc. Rigorous phase-scan measurements exhibit a phase-shift adjustment range of 0° to 360°, with a step of 5.625°, and a phase-shift accuracy of 0.5dB. Detailed data from gain-scan measurements show a gain-adjustment range of 0dB to 30dB, with a gain flatness of ± 0.5dB. Attenuation error is ≤ 1%. These test parameters perfectly align with the practical application requirements of the technical specifications. When compared to existing Ku-band PAs, our design reflects a deeper consideration of specific requirements in satellite communication, ensuring its outstanding performance and uniqueness. This PA features good stability, high linearity, low cost, and compact modularity, ensuring continuous and stable power output. These features position the proposed system as a leader within the market. Successful orbital deployment not only validates its operational stability; it also makes a significant contribution to the advancement of China's satellite PA technology, generating positive socio-economic benefits.

Optical Temperature-Sensing Performance of La2Ce2O7:Ho3+ Yb3+ Powders.

In this paper, La2Ce2O7 powders co-activated by Ho3+ and Yb3+ were synthesized by a high temperature solid-state reaction. Both Ho3+ and Yb3+ substitute the La3+ sites in the La2Ce2O7 lattice, where the Ho3+ concentration is 0.5 at.% and the Yb3+ concentration varies in the range of 10~18% at.%. Pumped by a 980 nm laser, the up-conversion (UC) green emission peak at 547 nm and the red emission at 661 nm were detected. When the doping concentration of Ho3+ and Yb3+ are 0.5 at.% and 14% at.%, respectively, the UC emission reaches the strongest intensity. The temperature-sensing performance of La2Ce2O7:Ho3+ with Yb3+ was studied in the temperature range of 303-483 K, where the highest relative sensitivity (Sr) is 0.0129 K-1 at 483 K. The results show that the powder La2Ce2O7:Ho3+, Yb3+ can be a potential candidate for remote temperature sensors.

Genome-wide identification and evolutionary analysis of the NRAMP gene family in the AC genomes of Brassica species.

BACKGROUND: Brassica napus, a hybrid resulting from the crossing of Brassica rapa and Brassica oleracea, is one of the most important oil crops. Despite its significance, B. napus productivity faces substantial challenges due to heavy metal stress, especially in response to cadmium (Cd), which poses a significant threat among heavy metals. Natural resistance-associated macrophage proteins (NRAMPs) play pivotal roles in Cd uptake and transport within plants. However, our understanding of the role of BnNRAMPs in B. napus is limited. Thus, this study aimed to conduct genome-wide identification and bioinformatics analysis of three Brassica species: B. napus, B. rapa, and B. oleracea. RESULTS: A total of 37 NRAMPs were identified across the three Brassica species and classified into two distinct subfamilies based on evolutionary relationships. Conservative motif analysis revealed that motif 6 and motif 8 might significantly contribute to the differentiation between subfamily I and subfamily II within Brassica species. Evolutionary analyses and chromosome mapping revealed a reduction in the NRAMP gene family during B. napus evolutionary history, resulting in the loss of an orthologous gene derived from BoNRAMP3.2. Cis-acting element analysis suggested potential regulation of the NRAMP gene family by specific plant hormones, such as abscisic acid (ABA) and methyl jasmonate (MeJA). However, gene expression pattern analyses under hormonal or stress treatments indicated limited responsiveness of the NRAMP gene family to these treatments, warranting further experimental validation. Under Cd stress in B. napus, expression pattern analysis of the NRAMP gene family revealed a decrease in the expression levels of most BnNRAMP genes with increasing Cd concentrations. Notably, BnNRAMP5.1/5.2 exhibited a unique response pattern, being stimulated at low Cd concentrations and inhibited at high Cd concentrations, suggesting potential response mechanisms distinct from those of other NRAMP genes. CONCLUSIONS: In summary, this study indicates complex molecular dynamics within the NRAMP gene family under Cd stress, suggesting potential applications in enhancing plant resilience, particularly against Cd. The findings also offer valuable insights for further understanding the functionality and regulatory mechanisms of the NRAMP gene family.

Structural identification and anti-neuroinflammatory effect of a heteropolysaccharide ATP50-3 from Acorus tatarinowii rhizome.

Acorus tatarinowii, a famous traditional Chinese medicine, is used for the clinical treatment of memory impairment and dementia. In this research, AT50, the crude polysaccharide extracted from A. tatarinowii rhizome, significantly improved the memory and learning ability of mice with Alzheimer's disease (AD) and exerted excellent anti-neuroinflammatory effects. More importantly, AT50 returned the levels of NO, TNF-α, IL-1ß, PGE-2, and IL-6 in AD mouse brains to normal levels. To identify the active ingredients in AT50, a heteropolysaccharide ATP50-3 was obtained from AT50. Structural analysis indicated ATP50-3 consisted of α-L-Araf-(1→, →2)-α-L-Araf-(1→, →3)-α-L-Araf-(1→, →5)-α-L-Araf-(1→, α-D-Xylp-(1→, →3,4)-ß-D-Xylp-(1→, →3)-α-D-Galp-(1→, →3,6)-α-D-Galp-(1→, →6)-4-OAc-α-D-Galp-(1→, →3,4,6)-α-D-Galp-(1→, →4)-α-D-Glcp-(1→, →2,3,6)-ß-D-Glcp-(1→, →4,6)-α-D-Manp-(1→, →3,4)-α-L-Rhap-(1→, →4)-α-D-GalpA-(1→, and →4)-α-D-GlcpA-(1 â†’ residues and terminated with Xyl and Ara. Additionally, ATP50-3 significantly inhibited the release of proinflammatory factors in lipopolysaccharide-stimulated BV2 cells. ATP50-3 may be an active constituent of AT50, responsible for its anti-neuroinflammatory effects, with great potential to treat AD.

Structural identification and anti-neuroinflammatory effects of a pectin-arabinoglucuronogalactan complex, AOPB-1-1, isolated from Asparagus officinalis.

Asparagus officinalis L. is a horticultural crop that contains a variety of bioactive compounds with anti-inflammatory effects. Aqueous extracts of A. officinalis can noticeably improve the learning and memory function of model mice. Herein, a pectin-arabinoglucuronogalactan complex (AOPB-1-1) with a relative molecular weight of 90.8 kDa was isolated from A. officinalis. The repeating structural unit of AOPB-1-1 was identified through monosaccharide composition, methylation analysis, uronic acid reduction, partial acid hydrolysis, and nuclear magnetic resonance spectroscopy. AOPB-1-1 contains the rhamnogalacturonan-I (RG-I) domain of pectin polysaccharides (PPs) and arabinoglucuronogalactan (AGG) regions. The backbone of the AGG region is composed of →3,6)-ß-D-Galp-(1→ and →4)-ß-D-Glcp-(1→ residues substituted at the 4-position to the →4)-α-D-GalAp-(1→ residues of the RG-I main chain. The anti-neuroinflammatory activity of AOPB-1-1 suggests that it can significantly reduce the content of inflammatory cytokines, including nitric oxide (NO), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) and inhibit the expression of inflammatory genes including cyclooxygenase-2 (COX2), nitric oxide synthase (iNOS), TNF-α, IL-6, and interleukin-1ß (IL-1ß) in LPS-stimulated BV2 cells. Furthermore, its inhibitory effects on TNF-α and IL-6 levels were even better than those of minocycline. The significant anti-neuroinflammatory activity of AOPB-1-1 suggests its applicability as a therapeutic option for the treatment of Alzheimer's disease.

Multivariate modular metabolic engineering and medium optimization for vitamin B12 production by Escherichia coli.

Vitamin B12 is a complex compound synthesized by microorganisms. The industrial production of vitamin B12 relies on specific microbial fermentation processes. E. coli has been utilized as a host for the de novo biosynthesis of vitamin B12, incorporating approximately 30 heterologous genes. However, a metabolic imbalance in the intricate pathway significantly limits vitamin B12 production. In this study, we employed multivariate modular metabolic engineering to enhance vitamin B12 production in E. coli by manipulating two modules comprising a total of 10 genes within the vitamin B12 biosynthetic pathway. These two modules were integrated into the chromosome of a chassis cell, regulated by T7, J23119, and J23106 promoters to achieve combinatorial pathway optimization. The highest vitamin B12 titer was attained by engineering the two modules controlled by J23119 and T7 promoters. The inclusion of yeast powder to the fermentation medium increased the vitamin B12 titer to 1.52 mg/L. This enhancement was attributed to the effect of yeast powder on elevating the oxygen transfer rate and augmenting the strain's isopropyl-ß-d-1-thiogalactopyranoside (IPTG) tolerance. Ultimately, vitamin B12 titer of 2.89 mg/L was achieved through scaled-up fermentation in a 5-liter fermenter. The strategies reported herein will expedite the development of industry-scale vitamin B12 production utilizing E. coli.

Sleep Quality and Suicidal Ideation in Adolescent Depression: A Chain Mediation Effect of Perceived Social Support and Resilience.

BACKGROUND: The prevalence of suicide is high among major depressive adolescents. Poor sleep quality has been documented as a significant risk factor for suicide, influencing perceived social support. Enhanced social support acts as a buffer against suicidal ideation and positively impacts resilience, reducing the prevalence of suicidal ideation. This reciprocal relationship between sleep quality, social support and resilience forms the basis for understanding the mechanisms contributing to suicidal ideation in major depressive adolescents. METHODS: A total of 585 major depressive adolescents aged 11 to 24 years was conducted to explore these associations. Assessments included the Pittsburgh Sleep Quality Index, Multidimensional Scale of Perceived Social Support, Connor-Davidson Resilience Scale and Beck Scale for Suicide Ideation. Pearson correlation and Model 6 in the SPSS program were employed for chain mediating tests. RESULTS: Better sleep quality positively predicted decreased suicide ideation (ß = 0.207, p < 0.01) and predicted lower perceived social support (ß = -0.226, p < 0.01) and resilience (ß = -0.355, p < 0.01). Perceived social support positively predicted increased resilience (ß = 0.422, p < 0.01) and negatively predicted suicide ideation (ß = -0.288, p < 0.01). Resilience negatively predicted suicide ideation (ß = -0.187, p < 0.01). Sleep quality indirectly predicted suicide ideation through perceived social support and resilience, with a mediation value of 0.0678 (95% CI [0.0359, 0.1060]), constituting 10.65% of the total effect. CONCLUSIONS: This study establishes that sleep quality indirectly predicts suicide ideation in major depressive adolescents, mediated independently by perceived social support and resilience.

Structural clarification of mannoglucan GSBP-2 from Ganoderma sinense and its effects on triple-negative breast cancer migration and invasion.

Ganoderma sinense, known as Lingzhi in China, is a medicinal fungus with anti-tumor properties. Herein, crude polysaccharides (GSB) extracted from G. sinense fruiting bodies were used to selectively inhibit triple-negative breast cancer (TNBC) cells. GSBP-2 was purified from GSB, with a molecular weight of 11.5 kDa and a composition of α-l-Fucp-(1→, ß-d-Glcp-(1→, ß-d-GlcpA-(1→, →3)-ß-d-Glcp-(1→, →3)-ß-d-GlcpA-(1→, →4)-α-d-Galp-(1→,→6)-ß-d-Manp-(1→, and →3,6)-ß-d-Glcp-(1→ at a ratio of 1.0:6.3:1.7:5.5:1.5:4.3:8.0:7.9. The anti-MDA-MB-231 cell activity of GSBP-2 was determined by methyl thiazolyl tetrazolium, colony formation, scratch wound healing, and transwell migration assays. The results showed that GSBP-2 could selectively inhibit the proliferation, migration, and invasion of MDA-MB-231 cells through the regulation of genes targeting epithelial-mesenchymal transition (i.e., Snail1, ZEB1, VIM, CDH1, CDH2, and MMP9) in the MDA-MB-231 cells. Furthermore, Western blotting results indicated that GSBP-2 could restrict epithelial-mesenchymal transition by increasing E-cadherin and decreasing N-cadherin expression through the PI3K/Akt pathway. GSBP-2 also suppressed the angiogenesis of human umbilical vein endothelial cells. In conclusion, GSBP-2 could inhibit the proliferation, migration, and invasion of MDA-MB-231 cells and showed significant anti-angiogenic ability. These findings indicate that GSBP-2 is a promising therapeutic adjuvant for TNBC.

Red Emitting Solid-State CDs/PVP with Hydrophobicity for Latent Fingerprint Detection.

Fluorescent carbon dots (CDs) are a new type of photoluminescent nanomaterial. Solid-state CDs usually undergo fluorescence quenching due to direct π-π* interactions and superabundant energy resonance transfer. Therefore, the preparation of solid-state fluorescent CDs is a challenge, especially the preparation of long wavelength solid-state CDs. In this research, long wavelength emission CDs were successfully synthesized by solvothermal methods, and the prepared CDs showed good hydrophobicity. The composite solid-state CDs/PVP (Polyvinyl pyrrolidone) can emit strong red fluorescence, and the quantum yield (QY) of the CDs/PVP powder reaches 18.9%. The prepared CDs/PVP solid-state powder was successfully applied to latent fingerprint detection. The results indicate that the latent fingerprints developed by CDs/PVP powder have a fine definition and high contrast visualization effect, which proves that the prepared CDs/PVP has great application potential in latent fingerprint detection. This study may provide inspiration and ideas for the design of new hydrophobic CDs.

Melatonin improves influenza virus infection-induced acute exacerbation of COPD by suppressing macrophage M1 polarization and apoptosis.

BACKGROUND: Influenza A viruses (IAV) are extremely common respiratory viruses for the acute exacerbation of chronic obstructive pulmonary disease (AECOPD), in which IAV infection may further evoke abnormal macrophage polarization, amplify cytokine storms. Melatonin exerts potential effects of anti-inflammation and anti-IAV infection, while its effects on IAV infection-induced AECOPD are poorly understood. METHODS: COPD mice models were established through cigarette smoke exposure for consecutive 24 weeks, evaluated by the detection of lung function. AECOPD mice models were established through the intratracheal atomization of influenza A/H3N2 stocks in COPD mice, and were injected intraperitoneally with melatonin (Mel). Then, The polarization of alveolar macrophages (AMs) was assayed by flow cytometry of bronchoalveolar lavage (BAL) cells. In vitro, the effects of melatonin on macrophage polarization were analyzed in IAV-infected Cigarette smoking extract (CSE)-stimulated Raw264.7 macrophages. Moreover, the roles of the melatonin receptors (MTs) in regulating macrophage polarization and apoptosis were determined using MTs antagonist luzindole. RESULTS: The present results demonstrated that IAV/H3N2 infection deteriorated lung function (reduced FEV20,50/FVC), exacerbated lung damages in COPD mice with higher dual polarization of AMs. Melatonin therapy improved airflow limitation and lung damages of AECOPD mice by decreasing IAV nucleoprotein (IAV-NP) protein levels and the M1 polarization of pulmonary macrophages. Furthermore, in CSE-stimulated Raw264.7 cells, IAV infection further promoted the dual polarization of macrophages accompanied with decreased MT1 expression. Melatonin decreased STAT1 phosphorylation, the levels of M1 markers and IAV-NP via MTs reflected by the addition of luzindole. Recombinant IL-1ß attenuated the inhibitory effects of melatonin on IAV infection and STAT1-driven M1 polarization, while its converting enzyme inhibitor VX765 potentiated the inhibitory effects of melatonin on them. Moreover, melatonin inhibited IAV infection-induced apoptosis by suppressing IL-1ß/STAT1 signaling via MTs. CONCLUSIONS: These findings suggested that melatonin inhibited IAV infection, improved lung function and lung damages of AECOPD via suppressing IL-1ß/STAT1-driven macrophage M1 polarization and apoptosis in a MTs-dependent manner. Melatonin may be considered as a potential therapeutic agent for influenza virus infection-induced AECOPD.

A hybrid RNA-protein biosensor for high-throughput screening of adenosylcobalamin biosynthesis.

Genetically encoded circuits have been successfully utilized to assess and characterize target variants with desirable traits from large mutant libraries. Adenosylcobalamin is an essential coenzyme that is required in many intracellular physiological reactions and is widely used in the pharmaceutical and food industries. High-throughput screening techniques capable of detecting adenosylcobalamin productivity and selecting superior adenosylcobalamin biosynthesis strains are critical for the creation of an effective microbial cell factory for the production of adenosylcobalamin at an industrial level. In this study, we developed an RNA-protein hybrid biosensor whose input part was an endogenous RNA riboswitch to specifically respond to adenosylcobalamin, the inverter part was an orthogonal transcriptional repressor to obtain signal inversion, and the output part was a fluorescent protein to be easily detected. The hybrid biosensor could specifically and positively correlate adenosylcobalamin concentrations to green fluorescent protein expression levels in vivo. This study also improved the operating concentration and dynamic range of the hybrid biosensor by systematic optimization. An individual cell harboring the hybrid biosensor presented over 20-fold higher fluorescence intensity than the negative control. Then, using such a biosensor combined with fluorescence-activated cell sorting, we established a high-throughput screening platform for screening adenosylcobalamin overproducers. This study demonstrates that this platform has significant potential to quickly isolate high-productive strains to meet industrial demand and that the framework is acceptable for various metabolites.

Assessment of ADRB1 polymorphism in patients with acute coronary syndrome treated with ticagrelor and aspirin.

Background: This study investigated the influence of ADRB1 gene rs1801253 polymorphism on the treatment response of ticagrelor and aspirin in patients with acute coronary syndrome (ACS). Methods: Genetic typing was detected by Sanger sequencing. Platelet inhibition was assessed using thromboelastography. Kaplan-Meier and Cox regression were applied for prognosis analysis. Results: Out of 200 participants, 94 cases with rs1801253-CC genotype and 106 cases with CG+GG genotype were found. There was no significant difference between the rs1801253-CC and CG+GG groups in the number of ST-segment elevation myocardial infarction, non-ST-segment elevation myocardial infarction and unstable angina patients. There was no statistical difference in the basic data of patients in the two groups in terms of age, sex, medical history and medicine use in the dominant model. The rs1801253-CC genotype was a risk prognostic factor for ACS patients based on the Cox regression analysis results. Conclusion: Detecting ADRB1 polymorphism is crucial for ACS patients undergoing treatment with ticagrelor and aspirin.

Metabolome and transcriptome analyses reveal changes of rapeseed in response to ABA signal during early seedling development.

Seed germination is an important development process in plant growth. The phytohormone abscisic acid (ABA) plays a critical role during seed germination. However, the mechanism of rapeseed in response to ABA is still elusive. In order to understand changes of rapeseed under exogenous ABA treatment, we explored differentially expressed metabolites (DEMs) and the differentially expressed genes (DEGs) between mock- and ABA-treated seedlings. A widely targeted LC-MS/MS based metabolomics were used to identify and quantify metabolic changes in response to ABA during seed germination, and a total of 186 significantly DEMs were identified. There are many compounds which are involved in ABA stimuli, especially some specific ABA transportation-related metabolites such as starches and lipids were screened out. Meanwhile, a total of 4440 significantly DEGs were identified by transcriptomic analyses. There was a significant enrichment of DEGs related to phenylpropanoid and cell wall organization. It suggests that exogenous ABA mainly affects seed germination by regulating cell wall loosening. Finally, the correlation analysis of the key DEMs and DEGs indicates that many DEGs play a direct or indirect regulatory role in DEMs metabolism. The integrative analysis between DEGs and DEMs suggests that the starch and sucrose pathways were the key pathway in ABA responses. The two metabolites from starch and sucrose pathways, levan and cellobiose, both were found significantly down-regulated in ABA-treated seedlings. These comprehensive metabolic and transcript analyses provide useful information for the subsequent post-transcriptional modification and post germination growth of rapeseed in response to ABA signals and stresses.