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The recombinant adeno-associated virus (rAAV) vector is among the most promising viral vectors in gene therapy. However, the limited manufacturing capacity in human embryonic kidney (HEK) cells is a barrier to rAAV commercialization. We investigated the impact of endoplasmic reticulum (ER) protein processing and apoptotic genes on transient rAAV production in HEK293 cells. We selected four candidate genes based on prior transcriptomic studies: XBP1, GADD34 / PPP1R15A, HSPA6, and BCL2. These genes were stably integrated into HEK293 host cells. Traditional triple-plasmid transient transfection was used to assess the vector production capability and the quality of both the overexpressed stable pools and the parental cells. We show that the overexpression of XBP1, HSPA6, and GADD34 increases rAAV productivity by up to 100% and increases specific rAAV productivity by up to 78% in HEK293T cells. Additionally, more prominent improvement associated with ER protein processing gene overexpression was observed when parental cell productivity was high, but no substantial variation was detected under low-producing conditions. We also confirmed genome titer improvement across different serotypes (AAV2 and AAV8) and different cell lines (HEK293T and HEK293); however, the extent of improvement may vary. This study unveiled the importance of ER protein processing pathways in viral particle synthesis, capsid assembly, and vector production. KEY POINTS: ⢠Upregulation of endoplasmic reticulum (ER) protein processing (XBP1, HSPA6, and GADD34) leads to a maximum 100% increase in rAAV productivity and a maximum 78% boost in specific rAAV productivity in HEK293T cells ⢠The enhancement in productivity can be validated across different HEK293 cell lines and can be used for the production of various AAV serotypes, although the extent of the enhancement might vary slightly ⢠The more pronounced improvements linked to overexpressing ER protein processing genes were observed when parental cell productivity was high, with minimal variation noted under low-producing conditions.
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Dependovirus , Retículo Endoplásmico , Vectores Genéticos , Proteína 1 de Unión a la X-Box , Humanos , Células HEK293 , Dependovirus/genética , Proteína 1 de Unión a la X-Box/genética , Proteína 1 de Unión a la X-Box/metabolismo , Retículo Endoplásmico/metabolismo , Vectores Genéticos/genética , Expresión Génica , Proteína Fosfatasa 1/genética , Proteína Fosfatasa 1/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/genética , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Cápside/metabolismoRESUMEN
Poly(ethylene terephthalate) (PET) is a common single-use plastic and a major contributor to plastic waste. PET upcycling through enzymatic depolymerization has drawn significant interests, but lack of robust enzymes in acidic environments remains a challenge. This study investigates in-situ product removal (ISPR) of protons from enzymatic PET depolymerization via a membrane reactor, focusing on the ICCG variant of leaf branch compost cutinase. More than two-fold improvements in overall PET depolymerization and terephthalic acid yields were achieved employing ISPR for an initial PET loading of 10 mgPET mlbuffer-1. The benefit of ISPR was reduced for a lower initial loading of 1 mgPET mlbuffer-1 due to decreased need for pH stabilization of the enzyme-containing solutions. A back-of-envelop analysis suggests that at a modest dilution ratio, ISPR could help achieve savings on caustic base solutions used for pH control in a bioreactor. Our study provides valuable insights for future ISPR developments for enzymatic PET depolymerization, addressing the pressing need for more sustainable solutions towards plastic recycling and environmental conservation.
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BACKGROUND: Soy isoflavones have been reported to exhibit anti-tumor effects. We hypothesize that genetic variants in soy isoflavone metabolism-related genes are associated with the risk of lung cancer. METHODS: A two-stage case-control study design was conducted in this study. The discovery stage included 300 lung cancer cases and 600 healthy controls to evaluate the association of candidate genetic variants with lung cancer risk. The validation stage involved 1200 cases and 1200 controls to validate the associations found. Furthermore, qPCR was performed to assess the mRNA expression levels of different genotypes of the SNP. ELISA was used to explore the association between genotype and soy isoflavone levels, as well as the association between soy isoflavone levels and lung cancer risk. RESULTS: A nonlinear association was observed between plasma soy isoflavone levels and lung cancer risk, with higher soy isoflavone levels associated with lower lung cancer risk (P < 0.001). The two-stage case-control study identified that UGT1A1 rs3755319 A > C was associated with decreased lung cancer risk (Recessive model: adjusted OR = 0.69, 95 %CI = 0.57-0.84, P < 0.001). Moreover, eQTL analysis showed that the expression level of UGT1A1 in the rs3755319 CC genotype was lower than in the AA + AC genotype (P < 0.05). The plasma concentration of soy isoflavones in the rs3755319 CC genotype was higher than in the AA + AC genotype (P = 0.008). CONCLUSIONS: We identified a potentially functional SNP, UGT1A1 rs3755319 A > C, as being associated with decreased lung cancer risk. Further experiments will be needed to explore the mechanisms underlying the observed associations.
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Predisposición Genética a la Enfermedad , Glucuronosiltransferasa , Glycine max , Isoflavonas , Neoplasias Pulmonares , Polimorfismo de Nucleótido Simple , Humanos , Isoflavonas/sangre , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/sangre , Estudios de Casos y Controles , Persona de Mediana Edad , Femenino , Masculino , Glycine max/genética , Glucuronosiltransferasa/genética , Anciano , Genotipo , Factores de RiesgoRESUMEN
BACKGROUND: Chronic obstructive pulmonary disease (COPD) and hyperuricaemia are both characterised by systemic inflammation. Preventing chronic diseases among the population with common metabolic abnormality is an effective strategy. However, the association of hyperuricaemia with the higher incidence and risk of COPD remains controversial. Therefore, replicated researches in populations with distinct characteristics or demographics are compellingly warranted. METHODS: This cohort study adopted a design of ambispective hospital-based cohort. We used propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) to minimise the effects of potential confounding factors. A Cox regression model and restricted cubic spline (RCS) model were applied further to assess the effect of serum urate on the risk of developing COPD. Finally, we conducted a two-sample Mendelian randomisation (MR) analysis to explore evidence of causal association. RESULTS: There is a higher incidence in the population with hyperuricaemia compared with the population with normal serum urate (22.29/1000 person-years vs 8.89/1000 person-years, p=0.009). This result is robust after performing PSM (p=0.013) and IPTW (p<0.001). The Cox model confirms that hyperuricaemia is associated with higher risk of developing COPD (adjusted HR=3.35 and 95% CI=1.61 to 6.96). Moreover, RCS shows that the risk of developing COPD rapidly increases with the concentration of serum urate when it is higher than the reference (420 µmol/L). Finally, in MR analysis, the inverse variance weighted method evidences that a significant causal effect of serum urate on COPD (OR=1.153, 95% CI=1.034 to 1.289) is likely to be true. The finding of MR is robust in the repeated analysis using different methods and sensitivity analysis. CONCLUSIONS: Our study provides convincing evidence suggesting a robust positive association between serum urate and the risk of developing COPD, and indicates that the population with hyperuricaemia is at high risk of COPD in the Chinese population who seek medical advice or treatment in the hospital.
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Hiperuricemia , Enfermedad Pulmonar Obstructiva Crónica , Humanos , Estudios de Cohortes , Ácido Úrico , Hiperuricemia/epidemiología , Hiperuricemia/genética , Enfermedad Pulmonar Obstructiva Crónica/epidemiología , Enfermedad Pulmonar Obstructiva Crónica/genética , HospitalesRESUMEN
For bridges with high automobile traffic, a large amount of vibration is generated daily due to cars driving over imperfectly level roads, and a vibration energy harvester can convert this energy into electrical energy, thus providing energy for devices such as bridge health sensors. However, the traditional single degree of freedom magnetic levitation vibration energy harvester (SMEH) has the disadvantage of low output power, so this research designs an improved dual degree of freedom magnetic levitation vibration energy harvester (DMEH), and a mathematical model of the energy harvester is built for simulation tests and an optimization model based on NSGA-II algorithm is developed for optimizing the structural parameters of the energy harvester. The experimental results show that the maximum total output power of DMEH and SMEH on CSSBB1, CSSBB2 and CSSBB3 are 48.7 mW, 36.8 mW, 25.4 mW and 27.2 mW, 21.5 mW, 14.9 mW, respectively, and the minimum total magnet volumes of both on CSSBB1, CSSBB2 and CSSBB3 are 268 cm3, 132 cm3, 219 cm3, 214 cm3, 86.2 cm3, 156 cm3. Based on the experimental data, it is found that the maximum output power of the optimal solution of DMEH is larger than that of SMEH for the selected simply supported girder bridge project, and the volume of the former is also larger than that of the latter, but the degree of increase can still be adapted to the application environment. The research results have some reference significance for improving the energy harvesting efficiency of bridge vibration energy harvesters.
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A new biomanufacturing platform combining intracellular metabolic engineering of the oleaginous yeast Yarrowia lipolytica and extracellular bioreaction engineering provides efficient bioconversion of plant oils/animal fats into high-value products. However, predicting the hydrodynamics and mass transfer parameters is difficult due to the high agitation and sparging required to create dispersed oil droplets in an aqueous medium for efficient yeast fermentation. In the current study, commercial computational fluid dynamic (CFD) solver Ansys CFX coupled with the MUSIG model first predicts two-phase system (oil/water and air/water) mixing dynamics and their particle size distributions. Then, a three-phase model (oil, air, and water) utilizing dispersed air bubbles and a polydispersed oil phase was implemented to explore fermenter mixing, gas dispersion efficiency, and volumetric mass transfer coefficient estimations (kL a). The study analyzed the effect of the impeller type, agitation speed, and power input on the tank's flow field and revealed that upward-pumping pitched blade impellers (PBI) in the top two positions (compared to Rushton-type) provided advantageous oil phase homogeneity and similar estimated kL a values with reduced power. These results show good agreement with the experimental mixing and kL a data.
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Reactores Biológicos , Hidrodinámica , Animales , FermentaciónRESUMEN
Microbial cell factories offer an eco-friendly alternative for transforming raw materials into commercially valuable products because of their reduced carbon impact compared to conventional industrial procedures. These systems often depend on lignocellulosic feedstocks, mainly pentose and hexose sugars. One major hurdle when utilizing these sugars, especially glucose, is balancing carbon allocation to satisfy energy, cofactor, and other essential component needs for cellular proliferation while maintaining a robust yield. Nearly half or more of this carbon is inevitably lost as CO2 during the biosynthesis of regular metabolic necessities. This loss lowers the production yield and compromises the benefit of reducing greenhouse gas emissions-a fundamental advantage of biomanufacturing. This review paper posits the perspectives of using CO2 from the atmosphere, industrial wastes, or the exhausted gases generated in microbial fermentation as a feedstock for biomanufacturing. Achieving the carbon-neutral or -negative goals is addressed under two main strategies. The one-step strategy uses novel metabolic pathway design and engineering approaches to directly fix the CO2 toward the synthesis of the desired products. Due to the limitation of the yield and efficiency in one-step fixation, the two-step strategy aims to integrate firstly the electrochemical conversion of the exhausted CO2 into C1/C2 products such as formate, methanol, acetate, and ethanol, and a second fermentation process to utilize the CO2-derived C1/C2 chemicals or co-utilize C5/C6 sugars and C1/C2 chemicals for product formation. The potential and challenges of using CO2 as a feedstock for future biomanufacturing of fuels and chemicals are also discussed.
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Omega-3 fatty acids, including alpha-linolenic acids (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA), have shown major health benefits, but the human body's inability to synthesize them has led to the necessity of dietary intake of the products. The omega-3 fatty acid market has grown significantly, with a global market from an estimated USD 2.10 billion in 2020 to a predicted nearly USD 3.61 billion in 2028. However, obtaining a sufficient supply of high-quality and stable omega-3 fatty acids can be challenging. Currently, fish oil serves as the primary source of omega-3 fatty acids in the market, but it has several drawbacks, including high cost, inconsistent product quality, and major uncertainties in its sustainability and ecological impact. Other significant sources of omega-3 fatty acids include plants and microalgae fermentation, but they face similar challenges in reducing manufacturing costs and improving product quality and sustainability. With the advances in synthetic biology, biotechnological production of omega-3 fatty acids via engineered microbial cell factories still offers the best solution to provide a more stable, sustainable, and affordable source of omega-3 fatty acids by overcoming the major issues associated with conventional sources. This review summarizes the current status, key challenges, and future perspectives for the biotechnological production of major omega-3 fatty acids.
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Poly(ethylene terephthalate) (PET) is one of the world's most widely used polyester plastics. Due to its chemical stability, PET is extremely difficult to hydrolyze in a natural environment. Recent discoveries in new polyester hydrolases and breakthroughs in enzyme engineering strategies have inspired enormous research on biorecycling of PET. This study summarizes our research efforts toward large-scale, efficient, and economical biodegradation of post-consumer waste PET, including PET hydrolase selection and optimization, high-yield enzyme production, and high-capacity enzymatic degradation of post-consumer waste PET. First, genes encoding PETase and MHETase from Ideonella sakaiensis and the ICCG variant of leaf-branch compost cutinase (LCCICCG ) were codon-optimized and expressed in Escherichia coli BL21(DE3) for high-yield production. To further lower the enzyme production cost, a pelB leader sequence was fused to LCCICCG so that the enzyme can be secreted into the medium to facilitate recovery. To help bind the enzyme on the hydrophobic surface of PET, a substrate-binding module in a polyhydroxyalkanoate depolymerase from Alcaligenes faecalis (PBM) was fused to the C-terminus of LCCICCG . The resulting four different LCCICCG variants (LCC, PelB-LCC, LCC-PBM, and PelB-LCC-PBM), together with PETase and MHETase, were compared for PET degradation efficiency. A fed-batch fermentation process was developed to produce the target enzymes up to 1.2 g L-1 . Finally, the best enzyme, PelB-LCC, was selected and used for the efficient degradation of 200 g L-1 recycled PET in a well-controlled, stirred-tank reactor. The results will help develop an economical and scalable biorecycling process toward a circular PET economy.
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Ácidos Ftálicos , Tereftalatos Polietilenos , Tereftalatos Polietilenos/química , Hidrolasas/química , Ácidos Ftálicos/química , Ácidos Ftálicos/metabolismo , EtilenosRESUMEN
Lithium-sulfur batteries (LSBs) have emerged as one of the ideal contenders for the upcoming generation of high energy storage devices due to their superb energy density. Nonetheless, the shuttle effect generated by intermediate lithium polysulfides (LiPSs) during cell cycling brings about capacity degradation and poor cycling stability of LSBs. Here, a versatile SrFe12O19 (FSO) and acetylene black (AB) modified PP separator is first presented to inhibit the shuttle effect. Thanks to the strong chemical interaction of Fe and Sr with polysulphides in FSO, it can trap LiPSs and provide catalytic sites for their conversion. Therefore, the cell using the FSO/AB@PP separator has a high initial discharge specific capacity (930 mA h g-1) at 2 C and lasts for 1000 cycles with a remarkably low fading rate (0.036% per cycle), while those using PE and AB@PP separators have inferior initial specific capacities (255 mA h g-1 and 652 mA h g-1, respectively) and fail within 600 cycles. This work proposes a novel approach for addressing the shuttle of LiPSs from a bimetallic oxide modified separator.
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Background: The imbalance of gut microbiota (GM) is associated with a higher risk of thrombosis in patients with atrial fibrillation (AF). Oral anticoagulants (OACs) have been found to significantly reduce the risk of thromboembolism and increase the risk of bleeding. However, the OAC-induced alterations in gut microbiota in patients with AF remain elusive. Methods: In this study, the microbial composition in 42 AF patients who received long-term OAC treatment (AF-OAC group), 47 AF patients who did not (AF group), and 40 volunteers with the risk of AF (control group) were analyzed by 16S rRNA gene sequencing of fecal bacterial DNA. The metagenomic functional prediction of major bacterial taxa was performed using the Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) software package. Results: The gut microbiota differed between the AF-OAC and AF groups. The abundance of Bifidobacterium and Lactobacillus decreased in the two disease groups at the genus level, but OACs treatment mitigated the decreasing tendency and increased beneficial bacterial genera, such as Megamonas. In addition, OACs reduced the abundance of pro-inflammatory taxa on the genus Ruminococcus but increased certain potential pathogenic taxa, such as genera Streptococcus, Escherichia-Shigella, and Klebsiella. The Subgroup Linear discriminant analysis effect size (LEfSe) analyses revealed that Bacteroidetes, Brucella, and Ochrobactrum were more abundant in the anticoagulated bleeding AF patients, Akkermansia and Faecalibacterium were more abundant in the non-anticoagulated-bleeding-AF patients. The neutrophil-to-lymphocyte ratio (NLR) was lower in the AF-OAC group compared with the AF group (P < 0.05). Ruminococcus was positively correlated with the NLR and negatively correlated with the CHA2DS2-VASc score (P < 0.05), and the OACs-enriched species (Megamonas and Actinobacteria) was positively correlated with the prothrombin time (PT) (P < 0.05). Ruminococcus and Roseburia were negatively associated with bleeding events (P < 0.05). Conclusions: Our study suggested that OACs might benefit AF patients by reducing the inflammatory response and modulating the composition and abundance of gut microbiota. In particular, OACs increased the abundance of some gut microbiota involved in bleeding and gastrointestinal dysfunction indicating that the exogenous supplementation with Faecalibacterium and Akkermansia might be a prophylactic strategy for AF-OAC patients to lower the risk of bleeding after anticoagulation.
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Fibrilación Atrial , Microbioma Gastrointestinal , Accidente Cerebrovascular , Humanos , Fibrilación Atrial/complicaciones , Fibrilación Atrial/tratamiento farmacológico , Fibrilación Atrial/inducido químicamente , Filogenia , ARN Ribosómico 16S/genética , Factores de Riesgo , Anticoagulantes/uso terapéutico , Hemorragia/inducido químicamente , Hemorragia/complicaciones , Administración Oral , Medición de RiesgoRESUMEN
More than 200 million tons of plant oils and animal fats are produced annually worldwide from oil, crops, and the rendered animal fat industry. Triacylglycerol, an abundant energy-dense compound, is the major form of lipid in oils and fats. While oils or fats are very important raw materials and functional ingredients for food or related products, a significant portion is currently diverted to or recovered as waste. To significantly increase the value of waste oils or fats and expand their applications with a minimal environmental footprint, microbial biomanufacturing is presented as an effective strategy for adding value. Though both bacteria and yeast can be engineered to use oils or fats as the biomanufacturing feedstocks, the yeast Yarrowia lipolytica is presented as one of the most attractive platforms. Y. lipolytica is oleaginous, generally regarded as safe, demonstrated as a promising industrial producer, and has unique capabilities for efficient catabolism and bioconversion of lipid substrates. This review summarizes the major challenges and opportunities for Y. lipolytica as a new biomanufacturing platform for the production of value-added products from oils and fats. This review also discusses relevant cellular and metabolic engineering strategies such as fatty acid transport, fatty acid catabolism and bioconversion, redox balances and energy yield, cell morphology and stress response, and bioreaction engineering. Finally, this review highlights specific product classes including long-chain diacids, wax esters, terpenes, and carotenoids with unique synthesis opportunities from oils and fats in Y. lipolytica.
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Yarrowia , Animales , Yarrowia/genética , Azúcares/metabolismo , Aceites/metabolismo , Terpenos/metabolismo , Ingeniería Metabólica , Ácidos Grasos/químicaRESUMEN
Current biomanufacturing facilities are mainly built for batch or fed-batch operations, which are subject to low productivities and do not achieve the great bioconversion potential of the rewired cells generated via modern biotechnology. Continuous biomanufacturing should be the future directions for high-yield and low-cost manufacturing of various fermentation products. This review discusses the major challenges and the strategies for continuous biomanufacturing with microbes, which include minimizing contamination risk, enhancing genetic stability over a long-term continuous operation, achieving high product titer, rate, and yield simultaneously by decoupling cell growth from product formation, and using modeling approach to accelerate research and development of continuous biomanufacturing. New strain designs and process engineering strategies, including integration with artificial intelligence, are also discussed for intelligent and the next generation of continuous biomanufacturing.
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Inteligencia Artificial , Reactores Biológicos , Biotecnología , Fermentación , ComercioRESUMEN
The plant-sourced polyketide triacetic acid lactone (TAL) has been recognized as a promising platform chemical for the biorefinery industry. However, its practical application was rather limited due to low natural abundance and inefficient cell factories for biosynthesis. Here, we report the metabolic engineering of oleaginous yeast Rhodotorula toruloides for TAL overproduction. We first introduced a 2-pyrone synthase gene from Gerbera hybrida (GhPS) into R. toruloides and investigated the effects of different carbon sources on TAL production. We then systematically employed a variety of metabolic engineering strategies to increase the flux of acetyl-CoA by enhancing its biosynthetic pathways and disrupting its competing pathways. We found that overexpression of ATP-citrate lyase (ACL1) improved TAL production by 45% compared to the GhPS overexpressing strain, and additional overexpression of acetyl-CoA carboxylase (ACC1) further increased TAL production by 29%. Finally, we characterized the resulting strain I12-ACL1-ACC1 using fed-batch bioreactor fermentation in glucose or oilcane juice medium with acetate supplementation and achieved a titer of 28 or 23 g/L TAL, respectively. This study demonstrates that R. toruloides is a promising host for the production of TAL and other acetyl-CoA-derived polyketides from low-cost carbon sources.
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Ingeniería Metabólica , Policétidos , Acetilcoenzima A , Carbono , Ingeniería Metabólica/métodos , Policétidos/metabolismo , Pironas , Rhodotorula , Levaduras/metabolismoRESUMEN
Melt extrusion pretreatment of poly(ethylene terephthalate) (PET) prior to enzymatic depolymerization with an unpurified leaf branch compost cutinase enzyme cocktail is explored to ascertain the efficiency gained by different processing methods on the enzymatic depolymerization of PET. Specific surface area (SSA) is investigated as a key factor in reducing depolymerization time. Higher SSA substrates (>5.6 mm2 mg-1 ) show higher depolymerization rates (≈0.88 g L-1 terephthalic acid [TPA] per day) and no induction phase, while lower SSA substrates (≈4.3, 4.4, and 5.6 mm2 mg-1 ) show, after an initial induction phase, similar depolymerization rates (≈0.46, 0.45, and 0.44 g L-1 TPA per day) despite increases in SSA of up to 30%. The mechanism of enzymatic depolymerization manifests in the appearance of anisotropic pitting. Longer incubation time used to overcome the induction phase in low SSA substrates allows for nearly full recovery of monomeric products, but manual pregrinding of extruded PET sharply increases SSA, depolymerization rate, and substrate crystallinity which may decrease the maximum recycled yield of the product materials. An estimate of the energy cost of increasing SSA is made and its effects on material properties are discussed. This work highlights key material structure and pretreatment aspects influencing the enzymatic recycling of PET.
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Ácidos Ftálicos , Tereftalatos Polietilenos , Etilenos , Tereftalatos Polietilenos/química , ReciclajeRESUMEN
Polyethylene terephthalate (PET) is one of the most commonly used polyester plastics worldwide but is extremely difficult to be hydrolyzed in a natural environment. PET plastic is an inexpensive, lightweight, and durable material, which can readily be molded into an assortment of products that are used in a broad range of applications. Most PET is used for single-use packaging materials, such as disposable consumer items and packaging. Although PET plastics are a valuable resource in many aspects, the proliferation of plastic products in the last several decades have resulted in a negative environmental footprint. The long-term risk of released PET waste in the environment poses a serious threat to ecosystems, food safety, and even human health in modern society. Recycling is one of the most important actions currently available to reduce these impacts. Current clean-up strategies have attempted to alleviate the adverse impacts of PET pollution but are unable to compete with the increasing quantities of PET waste exposed to the environment. In this review paper, current PET recycling methods to improve life cycle and waste management are discussed, which can be further implemented to reduce plastics pollution and its impacts on health and environment. Compared with conventional mechanical and chemical recycling processes, the biotechnological recycling of PET involves enzymatic degradation of the waste PET and the followed bioconversion of degraded PET monomers into value-added chemicals. This approach creates a circular PET economy by recycling waste PET or upcycling it into more valuable products with minimal environmental footprint.
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The aim of this study was to evaluate the characteristics of paediatric hand fractures (PHF) at a tertiary hospital in South China based on sex, age, mechanism of injury and anatomical region. A retrospective observational study was performed on children aged 15 years and younger who were referred for actual or suspected hand fractures between January 2016 and December 2020. Medical records and radiographs were reviewed for age at the time of injury, sex, site and fracture pattern and mechanism of injury. A total of 436 consecutive children with 478 hand fractures were reviewed. Hand fractures was more common in boys (281/436; 64.4%) than in girls (155/436; 35.6%), although most fractures occurred in children aged 0-3 years (198/436; 45.4%). Distal phalanges were the most commonly injured bones (184/478; 38.5%), and the base fractures were most common (151/476; 31.7%); the fifth digit was most commonly injured (150/478; 31.3%). Crush injuries were the leading cause of fracture in children younger than 6 years of age (207/325; 63.7%), whereas punch injuries were the major cause of injury in older age groups (55/153; 35.9%); 60.1% of the fractures were managed nonsurgically. This study showed patterns of PHF in a tertiary hospital in South China. It illustrates the local variability across sex, age group, injury type and injury mechanism. Such demographic data will be valuable for optimally resourcing healthcare systems locally and help guide prevention policies.
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Fracturas Óseas , Anciano , Niño , China/epidemiología , Femenino , Fracturas Óseas/diagnóstico por imagen , Fracturas Óseas/epidemiología , Fracturas Óseas/terapia , Humanos , Masculino , Derivación y Consulta , Estudios Retrospectivos , Centros de Atención TerciariaRESUMEN
Microbial synthesis of wax esters (WE) from low-cost renewable and sustainable feedstocks is a promising path to achieve cost-effectiveness in biomanufacturing. WE are industrially high-value molecules, which are widely used for applications in chemical, pharmaceutical, and food industries. Since the natural WE resources are limited, the WE production mostly rely on chemical synthesis from rather expensive starting materials, and therefore solution are sought from development of efficient microbial cell factories. Here we report to engineer the yeast Yarrowia lipolytica and bacterium Escherichia coli to produce WE at the highest level up to date. First, the key genes encoding fatty acyl-CoA reductases and wax ester synthase from different sources were investigated, and the expression system for two different Y. lipolytica hosts were compared and optimized for enhanced WE production and the strain stability. To improve the metabolic pathway efficiency, different carbon sources including glucose, free fatty acid, soybean oil, and waste cooking oil (WCO) were compared, and the corresponding pathway engineering strategies were optimized. It was found that using a lipid substrate such as WCO to replace glucose led to a 60-fold increase in WE production. The engineered yeast was able to produce 7.6 g/L WE with a yield of 0.31 (g/g) from WCO within 120 h and the produced WE contributed to 57% of the yeast DCW. After that, E. coli BL21(DE3), with a faster growth rate than the yeast, was engineered to significantly improve the WE production rate. Optimization of the expression system and the substrate feeding strategies led to production of 3.7-4.0 g/L WE within 40 h in a 1-L bioreactor. The predominant intracellular WE produced by both Y. lipolytica and E. coli in the presence of hydrophobic substrates as sole carbon sources were C36, C34 and C32, in an order of decreasing abundance and with a large proportion being unsaturated. This work paved the way for the biomanufacturing of WE at a large scale.
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Ésteres , Yarrowia , Biocombustibles , Escherichia coli/genética , Ácidos Grasos , Ingeniería Metabólica , Yarrowia/genéticaRESUMEN
BACKGROUND: Few studies have evaluated the clinical presentation, management, and outcomes of patients with end-stage renal disease (ESRD) presenting with acute aortic dissection (AAD) in real-world clinical practice. Thus, this study investigated the clinical characteristics, management, and outcomes of AAD patients with ESRD. METHODS: A total of 217 patients were included. We evaluated the differences in the clinical features, management, and in-hospital outcomes of patients with and without a history of ESRD presenting with AAD. RESULTS: A history of ESRD was present in 71 of 217 patients. Patients with ESRD had atypical clinical manifestations (p < 0.001) and were more likely to be managed medically compared with patients without ESRD (p = 0.002). Hypertension and type B aortic dissection were significantly more common among patients with ESRD. Moreover, patients with ESRD had lower leucocyte and platelet counts than patients without ESRD in laboratory findings (p < 0.001). However, hospitalization days and in-hospital mortality were similar between the two groups (p > 0.05). Multivariate analysis identified Type A aortic dissection as an independent predictor of in-hospital mortality among patients without ESRD (OR, 13.68; 95% CI, 1.92 to 98.90; P = 0.006). CONCLUSIONS: This study highlights differences in the clinical characteristics, management, and outcomes of AAD patients with ESRD. These patients usually have atypical symptoms and more comorbid conditions and are managed more conservatively. However, these patients have no in-hospital survival disadvantage over those without ESRD. Further studies are needed to better understand and optimize care for patients with ESRD presenting with AAD.