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The financing costs of green asset-backed securities (ABS) are deeply affected by the increased information asymmetry and greenwashing risk resulting from risk transferring in securitization. To attract potential investors, many ABS issuers obtain external certifications, yet it is unclear whether they pay off financially. Based on a sample of 588 green ABS issued in China for 2016-2022, this paper examines the impact of external certification in the form of green certification and reputation of financial intermediaries involved in the issuance on the yield discount of green ABS over the paired non-green ABS. The empirical findings show that both external certifications lower the greenium of green ABS by serving as favorable signals and mitigating greenwashing concerns, especially in non-financial industry and the securities exchange market. Moreover, the information asymmetry and credit risk of issuers enhance the pricing effect of financial intermediary certification but undermine that of green certification. Our findings provide valuable implications to facilitate the financing efficiency of green financial markets and promote global low-carbon transition.
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Certificação , China , Certificação/economia , Investimentos em Saúde/economiaRESUMO
Digital transformation has emerged as a key driver of high-quality enterprise development and an essential tool in forging an innovation-driven paradigm.Existing studies fail to delve into the specific mechanisms of their impact on firms' innovation performance, and views on their impact are divergent. Some studies suggest that digital transformation can enhance innovation performance, while others point out that it may have negative impacts, and cannot clearly answer how big data capabilities and organisational agility play a role in the digital transformation process. Therefore, based on dynamic capability theory and systems engineering theory, this study adopts the logical framework of "strategy-behaviour-performance" to systematically explore the process of digital transformation that enhances firms' innovation performance through the enhancement of big data capability and organisational agility. By empirically analysing the survey data of 476 manufacturing enterprises in China, the study reveals the chain-mediated effects of big data capability and organisational agility, and confirms the key roles of both in the transformation process. The findings suggest that digital transformation significantly improves firms' innovation performance, and that the dual mediating effects of big data capability and organisational agility are important links in its influencing mechanism. These findings not only provide empirical support for the theoretical model of digital transformation, but also provide practical guidance for enterprises to formulate strategies and optimise resource allocation in the digital era. We suggest that enterprises should strengthen the cultivation of big data capabilities and organisational agility while promoting digital transformation to better adapt to and lead market changes.
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A majority of flexible and wearable electronics require high operational voltage that is conventionally achieved by serial connection of battery unit cells using external wires. However, this inevitably decreases the energy density of the battery module and may cause additional safety hazards. Herein, a bipolar textile composite electrode (BTCE) that enables internal tandem-stacking configuration to yield high-voltage (6 to 12 V class) solid-state lithium metal batteries (SSLMBs) is reported. BTCE is comprised of a nickel-coated poly(ethylene terephthalate) fabric (NiPET) core layer, a cathode coated on one side of the NiPET, and a Li metal anode coated on the other side of the NiPET. Stacking BTCEs with solid-state electrolytes alternatively leads to the extension of output voltage and decreased usage of inert package materials, which in turn significantly boosts the energy density of the battery. More importantly, the BTCE-based SSLMB possesses remarkable capacity retention per cycle of over 99.98% over cycling. The composite structure of BTCE also enables outstanding flexibility; the battery keeps stable charge/discharge characteristics over thousands of bending and folding. BTCE shows great promise for future safe, high-energy-density, and flexible SSLMBs for a wide range of flexible and wearable electronics.
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Introduction: The escalating occurrence of infectious disease outbreaks in humans and animals necessitates innovative, effective, and integrated research to better comprehend their transmission and dynamics. Viral infection in livestock has led to profound economic losses globally. Pneumonia is the prevalent cause of death in sheep. However, very few studies exist regarding virus-related pathogens in sheep. Metagenomics sequencing technologies in livestock research hold significant potential to elucidate these contingencies and enhance our understanding. Methods: Therefore, this study aims to characterize respiratory viromes in paired nasal swabs from Inner Mongolian feedlot sheep in China using metaviromic sequencing. Through deep sequencing, de novo assembly, and similarity searches using translated protein sequences, several previously uncharacterized and known viruses were identified in this study. Results: Among these discoveries, a novel Bovine Rhinitis B Virus (BRBV) (BRBV-sheep) strain was serendipitously detected in the nasal swabs of domestic sheep (Ovis aries). To facilitate further molecular epidemiological studies, the entire genome of BRBV-sheep was also determined. Owing to the unique sequence characteristics and phylogenetic position of BRBV-sheep, genetically distinct lineages of BRBV in sheep may exist. A TaqMan-based qRT-PCR assay targeting the 3D polymerase gene was developed and used to screen 592 clinical sheep specimens. The results showed that 44.59% of the samples (264/592) were positive. These findings suggest that BRBV sheep are widespread among Inner Mongolian herds. Conclusion: This discovery marks the initial identification of BRBV in sheep within Inner Mongolia, China. These findings contribute to our understanding of the epidemiology and genetic evolution of BRBV. Recognizing the presence of BRBV in sheep informs strategies for disease management and surveillance and the potential development of targeted interventions to control its spread.
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Filogenia , Doenças dos Ovinos , Animais , China/epidemiologia , Ovinos , Doenças dos Ovinos/virologia , Doenças dos Ovinos/epidemiologia , Carneiro Doméstico , Nariz/virologia , Genoma Viral/genética , Sequenciamento de Nucleotídeos em Larga Escala , Metagenômica/métodosRESUMO
OBJECTIVE: To compare oncologic outcomes after laparoscopic or laparotomic surgery to treat epithelial ovarian carcinoma in FIGO stage I. DESIGN: Retrospective cohort study. SETTING: Gynecological cancer ward in a tertiary hospital. PARTICIPANTS: A total of 85 patients with FIGO stage I epithelial ovarian carcinoma who underwent laparoscopic staging surgery and 206 who underwent laparotomic staging surgery at West China Second Hospital, Sichuan University (Chengdu, China) between January 1, 2013 and December 31, 2019. INTERVENTIONS: laparoscopic surgery or laparotomic staging surgery. RESULTS: Before propensity score-based matching, the laparotomy group showed higher prevalence of preoperative elevated CA125 level (48.5% vs 35.3%, pâ¯=â¯.045) and tumors > 15 cm (27.2% vs 5.9%, p < .001). Multivariate analysis associated higher body mass index with better overall survival (adjusted HR 0.83, 95%CI 0.70-0.99, pâ¯=â¯.043). Among propensity score-matched patients (82 per group) who were matched to each other according to propensity scoring based on age, body mass index, CA125 level, largest tumor diameter, FIGO stage, history of abdominal surgery, and American Society of Anesthesiologists grade, the rate of progression-free survival at 5 years was similar between the laparoscopy group (87.1%, 95%CI 79.3-95.7%) and the laparotomy group (90.9%, 95%CI 84.7-97.6%, pâ¯=â¯.524), as was the rate of overall survival at 5 years (93.9%, 95%CI 88.0-100.0% vs 94.7%, 95%CI 89.8-99.9%, pâ¯=â¯.900). Regardless of whether patients were matched, the two groups showed similar rates of recurrence of 9-11% during follow-up lasting a median of 54.9 months. CONCLUSIONS: Rates of recurrence and survival may be similar between laparoscopy or laparotomy to treat stage I epithelial ovarian cancer. Since laparoscopy is associated with less bleeding and faster recovery, it may be a safe, effective alternative to laparotomy for appropriate patients.
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RATIONALE: Spinal cord ischemia injury is a serious complication after intra-aortic surgery, with a low incidence but high disability rate. However, patients often do not receive comprehensive treatment in the early stages of the disease. Therefore, active neurological intervention is needed to protect and prevent spinal cord ischemia during and after surgery. In this paper, rehabilitation program and imaging data of 2 cases with spinal cord ischemic injury are presented and discussed regarding causes, prevention and acute treatment with this disease, which could be referred by clinicians. PATIENT CONCERNS: Case report 1: A 69-year-old male patient underwent aortic arch aneurysm and thoracic endovascular aortic repair (coated stent) was performed under general anesthesia. Complete paralysis of both lower limbs, constipation, and urinary retention occurred after surgery and was subsequently referred to our rehabilitation department. Case report 2: A man aged 41 years experienced sudden chest pain with no dizziness or headache. Weakness of both lower limbs gradually appeared over 30 minutes with subsequent loss of consciousness. He was diagnosed with aortic dissection and underwent aortic stent implantation. Inpatient rehabilitation began systematically 3 months after discharge. DIAGNOSES: The 2 patients were diagnosed with paraplegia and spinal cord ischemic injury. INTERVENTIONS: The patients received strength and transfer training, sensory input, health mission, and activities of daily living. OUTCOMES: Patient 1 returned home without assistive devices and patient 2 returned home with wheelchair. LESSONS: Perioperative spinal cord protection is directly related to postoperative quality of life. Once the symptoms of spinal cord ischemic injury occur, cerebrospinal fluid drainage should be performed as soon as possible to increase mean arterial pressure. At the same time, methylprednisolone, ganglioside, anticoagulation, vasodilator drugs, and symptomatic supportive treatments are required. Intercostal artery and subclavian artery are reconstructed if necessary. Symptom stability flags referral to commence rehabilitation. Repetitive functional training is necessary to help patients return to the family and society as soon as possible.
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Isquemia do Cordão Espinal , Humanos , Masculino , Idoso , Isquemia do Cordão Espinal/etiologia , Adulto , Complicações Pós-Operatórias/etiologia , Paraplegia/etiologia , Dissecção Aórtica/cirurgia , Aneurisma da Aorta Torácica/cirurgia , Procedimentos Endovasculares/métodos , Procedimentos Endovasculares/efeitos adversosRESUMO
OBJECTIVE: To observe the effects of Zhoutian moxibustion on pain symptoms and serum inflammatory factors in patients with ankylosing spondylitis of cold-damp obstruction. METHODS: Eighty-four patients with ankylosing spondylitis of cold-damp obstruction were randomly divided into a Zhoutian moxibustion group (42 cases, 2 cases dropped out) and a governor vessel moxibustion group (42 cases, 2 cases dropped out, 1 case discontinued). Both groups were given oral administration of sulfasalazine enteric-coated tablets as basic treatment. The governor vessel moxibustion group was treated with moxibustion box from Dazhui (GV 14) to Yaoyangguan (GV 3), one hour per treatment; the Zhoutian moxibustion group was treated with moxibustion box from Tiantu (CV 22) to Zhongji (CV 3) in addition to the governor vessel moxibustion group, two hours per treatment. Both groups were treated once every 3 days, twice a week, for a total of 9 weeks. The pain symptom scores of the two groups were observed before treatment and at the 3rd, 6th, and 9th weeks into treatment. ELISA was used to detect the levels of serum interleukin (IL)-1ß, IL-18, and tumor necrosis factor-α (TNF-α) before and after treatment, and the clinical efficacy of the two groups was evaluated after treatment. RESULTS: Except for the joint pain scores at the 3rd week into treatment, the total scores and the each sub-item score of pain symptom in the two groups were lower than those before treatment at the 3rd, 6th, and 9th weeks into treatment (P<0.05); at the 3rd, 6th, and 9th weeks into treatment, the total scores of pain symptom and the scores of lumbar sacral pain, back pain, joint cold pain, and limited mobility in the Zhoutian moxibustion group were lower than those in the governor vessel moxibustion group (P<0.05). After treatment, the levels of serum IL-1ß, IL-18 and TNF-α in both groups were lower than those before treatment (P<0.05), and the levels of serum IL-1ß, IL-18, and TNF-α in the Zhoutian moxibustion group were lower than those in the governor vessel moxibustion group (P<0.05). The total effective rate was 90.0% (36/40) in the Zhoutian moxibustion group, which was higher than 76.9% (30/39) in the governor vessel moxibustion group (P<0.05). CONCLUSION: Zhoutian moxibustion could effectively improve various pain symptoms in patients with ankylosing spondylitis of cold-damp obstruction, and reduce the expression of inflammatory factors.
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Pontos de Acupuntura , Moxibustão , Espondilite Anquilosante , Fator de Necrose Tumoral alfa , Humanos , Masculino , Feminino , Adulto , Espondilite Anquilosante/terapia , Espondilite Anquilosante/complicações , Pessoa de Meia-Idade , Adulto Jovem , Fator de Necrose Tumoral alfa/sangue , Interleucina-1beta/sangue , Adolescente , Interleucina-18/sangue , Manejo da DorRESUMO
Introduction: Endogenous retroviruses (ERVs), which originated from exogenous retroviral infections of germline cells millions of years ago and were inherited by subsequent generations as per Mendelian inheritance patterns, predominantly comprise non-protein-coding sequences due to the accumulation of mutations, insertions, deletions, and truncations. Nevertheless, recent studies have revealed that ERVs play a crucial role in diverse biological processes by encoding various proteins. Methods: In this study, we successfully identified an ERV envelope (env) gene in a mink species. A phylogenetic tree of mink ERV-V env and reference sequences was constructed using Bayesian methods and maximum-likelihood inference. Results: Phylogenetic analyses indicated a significant degree of sequence conservation and positive selection within the env-surface open reading frame. Additionally, qRT-PCR revealed diverse patterns of mink ERV-V env expression in various tissues. The expression of mink ERV-V env gene in testicular tissue strongly correlated with the seasonal reproductive cycles of minks. Discussion: Our study suggests that the ERV-V env gene in mink may have been repurposed for host functions.
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Retrovirus Endógenos , Vison , Filogenia , Retrovirus Endógenos/genética , Animais , Vison/virologia , Proteínas do Envelope Viral/genética , Proteínas do Envelope Viral/metabolismo , Estações do Ano , Reprodução/genética , Masculino , Testículo/virologia , Teorema de BayesRESUMO
BACKGROUND AND AIMS: H-type hypertension is essential hypertension combined with high homocysteine, and both synergistically increase the risk of cardiovascular and cerebrovascular events. The aim of this study was to investigate the risk factors of H-type hypertension in Tibetan plateau population and correlation with MTHFR C677T gene. METHODS AND RESULTS: A multi-stage cluster random sampling method was used to select the research subjects in Tibet Autonomous Region from June 2020 to November 2021. Among Tibetans, the incidence of H-type hypertension accounted for 84.31% of hypertensive patients. The logistic regression analysis demonstrated that age, uric acid (UA), triglyceride (TG) and low-density lipoprotein cholesterol (LDL-C) were risk factors for the prevalence of H-type hypertension, the OR (95% CI) was 1.083(1.073-1.094), 1.002(1.001-1.004), 1.240(1.050-1.464) and 2.274(1.432-3.611), respectively. MTHFR C677T TT genotype patients with H-type hypertension OR (95% CI) was 1.629(1.004-2.643). Based on this, a nomogram model was established, and the reliability of the model was proved by area under ROC curve, Brier score and average absolute error. The model's results indicate that for every five years of age, the score increases by 6 points; for a 2mmol/L increase in TG, the score increases by 5.5 points; for a 1mmol/L increase in LDL-C, the score increases by 10 points; and individuals with the TT genotype receive 8 points. The higher the score, the greater the risk of disease. CONCLUSION: The MTHFR C677T TT genotype is a risk locus for Tibetan patients with H-type hypertension, with age, TG, and LDL-C were identified as risk factors for the disease.
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Predisposição Genética para Doença , Metilenotetra-Hidrofolato Redutase (NADPH2) , Humanos , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Tibet/epidemiologia , Feminino , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Medição de Risco , Adulto , Prevalência , Fenótipo , Hipertensão Essencial/genética , Hipertensão Essencial/diagnóstico , Hipertensão Essencial/epidemiologia , Hipertensão Essencial/fisiopatologia , Pressão Sanguínea/genética , Idoso , Incidência , Polimorfismo de Nucleotídeo Único , Homocisteína/sangue , Hiper-Homocisteinemia/genética , Hiper-Homocisteinemia/diagnóstico , Hiper-Homocisteinemia/epidemiologia , Hiper-Homocisteinemia/sangue , Hipertensão/genética , Hipertensão/diagnóstico , Hipertensão/epidemiologia , Hipertensão/fisiopatologiaRESUMO
Bacterial intestinal inflammation is a common disease of yellow catfish (Pelteobagrus fulvidraco) in high-density aquaculture. Understanding the interactions between host and intestinal bacteria is helpful to intestinal inflammatory disease control. Here, we constructed a model of intestinal inflammation after Aeromonas hydrophila infection in yellow catfish, and characterized variations in gene expression and microbiome in the gut through high-throughput sequencing. Furthermore, host gene-microbiome interactions were identified. Histology observation showed disordered distribution of columnar epithelial cells and decrease of goblet cells in intestine. A total of 4741 genes showed differentially expression, mostly in comparisons between 12 hpi group with each other groups respectively, including control, 24 hpi and 48 hpi groups. These genes were enriched in immune-related pathways including the IL-17 signaling pathway, triggering strong inflammatory response at the invading stage within 12 h. Subsequently, the host strengthened energy consumption by activating carbohydrate and lipid metabolism pathways to repair the intestinal mucosal immune defense line. In addition, fish with A. hydrophila infection show decreased richness of gut microbial, reduced relative abundance of probiotics including Akkermansia, and elevated pathogenic bacteria such as Plesimonas. An integrative analysis identified A. hydrophila-related genes, such as il22 and stat3, for which expression level is close associated with the shift of A. hydrophila-related bacteria relative abundance, such as Akkermansia and Cetobacterium. Aside from picturing the variations of intestine gene expression and mucosal microbiome of yellow catfish coping with A. hydrophila infection, our study probed the underlying host-microbe interactions in A. hydrophila infection induced intestinal inflammatory, providing new insights for disease control in aquaculture.
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Aeromonas hydrophila , Peixes-Gato , Doenças dos Peixes , Microbioma Gastrointestinal , Infecções por Bactérias Gram-Negativas , Animais , Aeromonas hydrophila/fisiologia , Peixes-Gato/imunologia , Peixes-Gato/genética , Infecções por Bactérias Gram-Negativas/imunologia , Infecções por Bactérias Gram-Negativas/veterinária , Doenças dos Peixes/imunologia , Doenças dos Peixes/microbiologiaRESUMO
Gradual disability of Zn anode and high negative/positive electrode (N/P) ratio usually depreciate calendar life and energy density of aqueous Zn batteries (AZBs). Herein, within original Zn2+-free hydrated electrolytes, a steric hindrance/electric field shielding-driven "hydrophobic ion barrier" is engineered towards ultradurable (002) plane-exposed Zn stripping/plating to solve this issue. Guided by theoretical simulations, hydrophobic adiponitrile (ADN) is employed as a steric hindrance agent to ally with inert electric field shielding additive (Mn2+) for plane adsorption priority manipulation, thereby constructing the "hydrophobic ion barrier". This design robustly suppresses the (002) plane/dendrite growth, enabling ultradurable (002) plane-exposed dendrite-free Zn stripping/plating. Even being cycled in ZnâZn symmetric cell over 2150 h at 0.5 mA cm-2, the efficacy remains well-kept. Additionally, ZnâZn symmetric cells can be also stably cycled over 918 h at 1 mA cm-2, verifying uncompromised Zn stripping/plating kinetics. As-assembled anode-less ZnâVOPO4·2H2O full cells with a low N/P ratio (2:1) show a high energy density of 75.2 Wh kg-1full electrode after 842 cycles at 1 A g-1, far surpassing counterparts with thick Zn anode and low cathode loading mass, featuring excellent practicality. This study opens a new avenue by robust "hydrophobic ion barrier" design to develop long-life anode-less Zn batteries.
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Hydrogel electrolytes (HEs) hold great promise in tackling severe issues emerging in aqueous zinc-ion batteries, but the prevalent salting-out effect of kosmotropic salt causes low ionic conductivity and electrochemical instability. Herein, a subtle molecular bridging strategy is proposed to enhance the compatibility between PVA and ZnSO4 from the perspective of hydrogen-bonding microenvironment re-construction. By introducing urea containing both an H-bond acceptor and donor, the broken H-bonds between PVA and H2O, initiated by the SO42--driven H2O polarization, could be re-united via intense intermolecular hydrogen bonds, thus leading to greatly increased carrying capacity of ZnSO4. The urea-modified PVA-ZnSO4 HEs featuring a high ionic conductivity up to 31.2 mS cm-1 successfully solves the sluggish ionic transport dilemma at the solid-solid interface. Moreover, an organic solid-electrolyte-interphase can be derived from the in-situ electro-polymerization of urea to prohibit H2O-involved side reactions, thereby prominently improving the reversibility of Zn chemistry. Consequently, Zn anodes witness an impressive lifespan extension from 50 h to 2200 h at 0.1 mA cm-2 while the Zn-I2 full battery maintains a remarkable Coulombic efficiency (>99.7%) even after 8000 cycles. The anti-salting-out strategy proposed in this work provides an insightful concept for addressing the phase separation issue of functional HEs.
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High-yield dairy cows typically undergo intense cellular metabolism, leading to oxidative stress in their mammary tissues. Our study found that these high-yield cows had significantly elevated levels of hydrogen peroxide (H2O2), lipoperoxidase, and total antioxidant capacity in their blood, compared with ordinary cows. This increased oxidative stress is associated with heightened expression of genes such as GCLC, GCLM and SIRT1 and proteins such as SIRT1 in the mammary tissue of high-yield cows. MAC-T cells were stimulated with H2O2 at a concentration equal to the average H2O2 level in the serum of ethically high-yielding cows, as detected by an assay kit. Our observations revealed that short-term exposure (12 h) to H2O2 upregulated the expression of SIRT1 gene and protein. It also increased gene expression for SOD2, CAT, GCLC, GCLM, PGC-1α, and NQO1, elevated the phosphorylation of AMPK, and enhanced protein expression of PGC-1α, NQO1, Nrf2, and HO-1, while reducing the phosphorylation of NF-κB. Additionally, short-term H2O2 stimulation resulted in increased total antioxidant capacity, SOD, GSH, and CAT levels in the mammary epithelial cells of dairy cows. In contrast, prolonged exposure to H2O2 (24 h) yielded opposite results, indicating reduced antioxidant capacity. Further investigation showed that SIRT1 inhibitor (EX 527) could reverse the enhanced cellular antioxidant capacity triggered by short-term oxidative stress. However, it is crucial to note that while 12 h H2O2 stimulation improved antioxidant capacity, reactive oxygen species (ROS) and malondialdehyde (MDA) levels inside the cell gradually increased over time, suggesting greater damage under long-term stimulation. Conversely, the SIRT1 activator (SRT 2104) could reverse the reduced cellular antioxidant capacity caused by long-term oxidative stress and significantly inhibit the accumulation of ROS and MDA. Notably, SRT 2104 demonstrated similar effects in MAC-T cells during lactation. In summary, SIRT1 plays a crucial role in regulating the antioxidant capacity of mammary epithelial cells in dairy cows. This discovery provides valuable insights into the antioxidant mechanisms of mammary cells, which can serve as a theoretical foundation for future mammary health strategies.
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L-Arabinose isomerase (L-AI) has been commonly used as an efficient biocatalyst to produce D-tagatose via the isomerization of D-galactose. However, it remains a significant challenge to efficiently synthesize D-tagatose using the native (wild type) L-AI at an industrial scale. Hence, it is extremely urgent to redesign L-AI to improve its catalytic efficiency towards D-galactose, and herein a structure-based molecular modification of Lactobacillus plantarum CY6 L-AI (LpAI) was performed. Among the engineered LpAI, both F118M and F279I mutants showed an increased D-galactose isomerization activity. Particularly, the specific activity of double mutant F118M/F279I towards D-galactose was increased by 210.1% compared to that of the wild type LpAI (WT). Besides the catalytic activity, the substrate preference of F118M/F279I was also largely changed from L-arabinose to D-galactose. In the enzymatic production of D-tagatose, the yield and conversion ratio of F118M/F279I were increased by 81.2% and 79.6%, respectively, compared to that of WT. Furthermore, the D-tagatose production of whole cells expressing F118M/F279I displayed about 2-fold higher than that of WT cell. These results revealed that the designed site-directed mutagenesis is useful for improving the catalytic efficiency of LpAI towards D-galactose.
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Ergothioneine (EGT) is a naturally occurring derivative of histidine with diverse applications in the medicine, cosmetic, and food industries. Nevertheless, its sustainable biosynthesis faces hurdles due to the limited biosynthetic pathways, complex metabolic network of precursors, and high cost associated with fermentation. Herein, efforts were made to address these limitations first by reconstructing a novel EGT biosynthetic pathway from Methylobacterium aquaticum in Escherichia coli and optimizing it through plasmid copy number. Subsequently, the supply of precursor amino acids was promoted by engineering the global regulator, recruiting mutant resistant to feedback inhibition, and blocking competitive pathways. These metabolic modifications resulted in a significant improvement in EGT production, increasing from 35 to 130 mg/L, representing a remarkable increase of 271.4%. Furthermore, an economical medium was developed by replacing yeast extract with corn steep liquor, a byproduct of wet milling of corn. Finally, the production of EGT reached 595 mg/L with a productivity of 8.2 mg/L/h by exploiting fed-batch fermentation in a 10 L bioreactor. This study paves the way for exploring and modulating a de novo biosynthetic pathway for efficient and low-cost fermentative production of EGT.
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Vias Biossintéticas , Ergotioneína , Escherichia coli , Fermentação , Engenharia Metabólica , Ergotioneína/biossíntese , Ergotioneína/metabolismo , Escherichia coli/genética , Escherichia coli/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Reatores BiológicosRESUMO
ß-Alanine, a valuable ß-type amino acid, is experiencing increased demand due to its multifaceted applications in food flavoring, nutritional supplements, pharmaceuticals, and the chemical industry. Nevertheless, the sustainable biosynthesis of ß-alanine currently faces challenges due to the scarcity of robust strains, attributed to the complexities of modulating multiple genes and the inherent physiological constraints. Here, systems metabolic engineering was implemented in Escherichia coli to overcome these limitations. First, an efficient l-aspartate-α-decarboxylase (ADC) was recruited for ß-alanine biosynthesis. To conserve phosphoenolpyruvate flux, we subsequently modified the endogenous glucose assimilation system by inactivating the phosphotransferase system (PTS) and introducing an alternative non-PTS system, which increased ß-alanine production to 1.70 g/L. The supply of key precursors, oxaloacetate and l-aspartate, was synergistically improved through comprehensive modulation, including strengthening main flux and blocking bypass metabolism, which significantly increased the ß-alanine titer to 3.43 g/L. Next, the expression of ADC was optimized by promoter and untranslated region (UTR) engineering. Further transport engineering, which involved disrupting ß-alanine importer CycA and heterologously expressing ß-alanine exporter NCgI0580, improved ß-alanine production to 8.48 g/L. Additionally, corn steep liquor was used to develop a cost-effective medium. The final strain produced 74.03 g/L ß-alanine with a yield of 0.57 mol/mol glucose during fed-batch fermentation.
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Escherichia coli , Fermentação , Glucose , Engenharia Metabólica , beta-Alanina , beta-Alanina/metabolismo , Escherichia coli/genética , Escherichia coli/metabolismo , Glucose/metabolismo , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Glutamato Descarboxilase/genética , Glutamato Descarboxilase/metabolismoRESUMO
As cancer continues to rise globally, there is growing interest in discovering novel methods for prevention and treatment. Due to the limitations of traditional cancer therapies, there has been a growing emphasis on investigating herbal remedies and exploring their potential synergistic effects when combined with chemotherapy drugs. Cinnamaldehyde, derived from cinnamon, has gained significant attention for its potential role in cancer prevention and treatment. Extensive research has demonstrated that cinnamaldehyde exhibits promising anticancer properties by modulating various cellular processes involved in tumor growth and progression. However, challenges and unanswered questions remain regarding the precise mechanisms for its effective use as an anticancer agent. This article aims to explore the multifaceted effects of cinnamaldehyde on cancer cells and shed light on these existing issues. Cinnamaldehyde has diverse anti-cancer mechanisms, including inducing apoptosis by activating caspases and damaging mitochondrial function, inhibiting tumor angiogenesis, anti-proliferation, anti-inflammatory and antioxidant. In addition, cinnamaldehyde also acts as a reactive oxygen species scavenger, reducing oxidative stress and preventing DNA damage and genomic instability. This article emphasizes the promising therapeutic potential of cinnamaldehyde in cancer treatment and underscores the need for future research to unlock novel mechanisms and strategies for combating cancer. By providing valuable insights into the role and mechanism of cinnamaldehyde in cancer, this comprehensive understanding paves the way for its potential as a novel therapeutic agent. Overall, cinnamaldehyde holds great promise as an anticancer agent, and its comprehensive exploration in this article highlights its potential as a valuable addition to cancer treatment options.
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Acroleína , Neoplasias , Acroleína/análogos & derivados , Acroleína/farmacologia , Acroleína/química , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Animais , Apoptose/efeitos dos fármacos , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Dano ao DNA/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismoRESUMO
Despite considerable research efforts, lipase catalysis in a fluid milk system with aqueous multi-component mixtures containing multiple microphases, remains challenging. Pickering interfacial biocatalysis (PIB) platforms are typically fabricated with organic solvents/lipids and water. Whether a PIB with excellent catalytic performance can be constructed in complex milk mixtures remains unknown. Here, we challenged PIB with skim milk, and a small amount of flaxseed oil, and phytosterols as a model system for transesterification and lipolysis to enhance quality and flavor. The amino-modified mesoporous silica spheres (MSS-N) were employed as an emulsifier and carrier of lipase AYS (AYS@MSS-N). The conversion of phytosterol esters reached 75.5% at 1.5 h and prepared phytosterol ester-fortified milk with a content of 1.0 g/100 mL. The relative conversion rate remained above 70% after 6 cycles. In addition, the fortified milk showed an intensified and favorable effect on sensory traits through volatile flavor composition analysis. The findings provide a versatile alternative for PIB applications in complex environments, i.e., milk, which might inspire a new bioprocess strategy for dairy products.
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Cyclin-dependent kinase 9 (CDK9) plays a role in transcriptional regulation, which had become an attractive target for discovery of antitumor agent. In this work, beyond traditional CDK9 inhibitor with bidentate ligands in ATP binding domain, a series of novel CDK9 inhibitor with tridentate ligand were designed and synthesized. Surprisingly, this unique tridentate ligand structure endows better CDK9 inhibition selectivity compared to other CDK subtypes, and the lead candidate compound Z4-7a showed effective proliferation inhibition in HCT116 cells with acceptable pharmacokinetic properties. Research on the mechanism indicated that Z4-7a could induce apoptosis in the HCT116 cell line by inhibiting phosphorylation of RNA polymerase II at Ser2, which resulted in the inhibition of apoptosis-related genes and proteins expression. In brief, introduction of tridentate ligand might work as a promising strategy for the development of novel selective CDK9 inhibitor.