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The prominence and versatility of propargylic fluorides in medicinal chemistry, coupled with the potency of F/H and F/OH bioisosterism, has created a powerful impetus to develop efficient methods to facilitate their construction. Motivated by the well-established conversion of propargylic alcohols to allenes, an operationally simple, organocatalysis-based strategy to process these abundant unsaturated precursors to propargylic fluorides would be highly enabling: this would consolidate the bioisosteric relationship that connects propargylic alcohols and fluorides. Herein, we describe a highly regioselective fluorination of unactivated allenes based on I(I)/I(III) catalysis in the presence of an inexpensive HF source that serves a dual role as both nucleophile and Brønsted acid activator. This strategy enables a variety of secondary and tertiary propargylic fluorides to be prepared: these motifs are prevalent across the bioactive small molecule spectrum. Facile product derivatisation, concise synthesis of multi-vicinal fluorinated products together with preliminary validation of enantioselective catalysis are disclosed. The expansive potential of this platform is also demonstrated through the highly regioselective organocatalytic oxidation, chlorination and arylation of allenes. It is envisaged that the transformation will find application in molecular design and accelerate the exploration of organofluorine chemical space.
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Purpose: This study investigated whether RNA-Seq-based endometrial receptivity test (rsERT)-which provides precision for the optimal hour of the window of implantation (WOI)-can improve clinical outcomes of frozen embryo transfer (FET) cycles in patients with a history of repeated implantation failure (RIF). Methods: Patients with a history of RIF who received at least one autologous high-quality blastocyst during the subsequent FET cycle were retrospectively enrolled and divided into two groups: rsERT and FET, comprising patients who underwent rsERT-guided pET (n=115) and standard FET without rsERT (n=272), respectively. Results: In the rsERT group, 39.1% (45/115) of patients were receptive. rsERT patients showed a higher probability of achieving both positive human chorionic gonadotropin (63.5% vs. 51.5%, P=0.03) and clinical pregnancy (54.8% vs. 38.6%, P=0.003) rates. In subgroup analysis, rsERT patients with non-receptive results had higher clinical pregnancy rates than patients undergoing FET (58.6% vs. 38.6%, P=0.003). rsERT patients with receptive results guided by rsERT with a precise WOI time had higher, although non-significant, clinical pregnancy rates (48.9% vs. 38.6%, P=0.192) than patients who underwent standard-time FET. Conclusion: Hourly precise rsERT can significantly improve the probability of achieving clinical pregnancy in patients with RIF, especially in those with non-receptive rsERT results.
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Implantación del Embrión , Transferencia de Embrión , Índice de Embarazo , Humanos , Femenino , Transferencia de Embrión/métodos , Embarazo , Adulto , Estudios Retrospectivos , Fertilización In Vitro/métodos , Endometrio , Resultado del TratamientoRESUMEN
Goos-Hänchen shift of total internal reflection (TIR) is the light beam movement without external driving, so envisioned to have potential manipulation of optical beams. In this article, with a silicon-on-insulator (SOI) waveguide corner structure, a variable equivalent permittivity of guided wave is modelled, and then the equivalent electric polarizabilities and the Goos-Hänchen shift of guided wave are modelled. Consequently, with a 2.0-µm SOI waveguide corner structure and an abrupt phase change of â¼0.5π caused by a vertically inserted metasurface of nanoscale semi-spheres having a 450-nm radius can reach the GH shifts of 2.1â µm for TE- and TM-mode, respectively, which are verified by both the FDTD simulation results of 1.93â µm with a reflectivity of about 62% and the experimental results of 2.0â µm with â¼60%. Therefore, this work has efficiently modelled the optical feature response of semi-sphere metasurface to guided wave and the active manipulation for the GH shifts of guided-wave, opening more opportunities to develop the new functionalities and devices for Si-based photonic integrated circuit (PIC) applications.
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BACKGROUND: Hemorrhagic fever with renal syndrome (HFRS) continues to pose a significant public health threat to the population in China. Previous epidemiological evidence indicates that HFRS is climate sensitive and influenced by meteorological factors. However, past studies either focused on too-narrow geographical regions or investigated time periods that were too early. There is an urgent need for a comprehensive analysis to interpret the epidemiological patterns of meteorological factors affecting the incidence of HFRS across diverse climate zones. OBJECTIVE: In this study, we aimed to describe the overall epidemic characteristics of HFRS and explore the linkage between monthly HFRS cases and meteorological factors at different climate levels in China. METHODS: The reported HFRS cases and meteorological data were collected from 151 cities in China during the period from 2015 to 2021. We conducted a 3-stage analysis, adopting a distributed lag nonlinear model and a generalized additive model to estimate the interactions and marginal effects of meteorological factors on HFRS. RESULTS: This study included a total of 63,180 cases of HFRS; the epidemic trends showed seasonal fluctuations, with patterns varying across different climate zones. Temperature had the greatest impact on the incidence of HFRS, with the maximum hysteresis effects being at 1 month (-19 ºC; relative risk [RR] 1.64, 95% CI 1.24-2.15) in the midtemperate zone, 0 months (28 ºC; RR 3.15, 95% CI 2.13-4.65) in the warm-temperate zone, and 0 months (4 ºC; RR 1.72, 95% CI 1.31-2.25) in the subtropical zone. Interactions were discovered between the average temperature, relative humidity, and precipitation in different temperature zones. Moreover, the influence of precipitation and relative humidity on the incidence of HFRS had different characteristics under different temperature layers. The hysteresis effect of meteorological factors did not end after an epidemic season, but gradually weakened in the following 1 or 2 seasons. CONCLUSIONS: Weather variability, especially low temperature, plays an important role in epidemics of HFRS in China. A long hysteresis effect indicates the necessity of continuous intervention following an HFRS epidemic. This finding can help public health departments guide the prevention and control of HFRS and develop strategies to cope with the impacts of climate change in specific regions.
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Ciudades , Epidemias , Fiebre Hemorrágica con Síndrome Renal , Conceptos Meteorológicos , Fiebre Hemorrágica con Síndrome Renal/epidemiología , Humanos , China/epidemiología , Estudios Retrospectivos , Factores de Riesgo , Ciudades/epidemiología , Masculino , Femenino , Incidencia , AdultoRESUMEN
Continuous monitoring of biomarkers at locations adjacent to targeted internal organs can provide actionable information about postoperative status beyond conventional diagnostic methods. As an example, changes in pH in the intra-abdominal space after gastric surgeries can serve as direct indicators of potentially life-threatening leakage events, in contrast to symptomatic reactions that may delay treatment. Here, we report a bioresorbable, wireless, passive sensor that addresses this clinical need, designed to locally monitor pH for early detection of gastric leakage. A pH-responsive hydrogel serves as a transducer that couples to a mechanically optimized inductor-capacitor circuit for wireless readout. This platform enables real-time monitoring of pH with fast response time (within 1 hour) over a clinically relevant period (up to 7 days) and timely detection of simulated gastric leaks in animal models. These concepts have broad potential applications for temporary sensing of relevant biomarkers during critical risk periods following diverse types of surgeries.
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Implantes Absorbibles , Transductores , Animales , Tecnología Inalámbrica , Concentración de Iones de Hidrógeno , BiomarcadoresRESUMEN
Monitoring homeostasis is an essential aspect of obtaining pathophysiological insights for treating patients. Accurate, timely assessments of homeostatic dysregulation in deep tissues typically require expensive imaging techniques or invasive biopsies. We introduce a bioresorbable shape-adaptive materials structure that enables real-time monitoring of deep-tissue homeostasis using conventional ultrasound instruments. Collections of small bioresorbable metal disks distributed within thin, pH-responsive hydrogels, deployed by surgical implantation or syringe injection, allow ultrasound-based measurements of spatiotemporal changes in pH for early assessments of anastomotic leaks after gastrointestinal surgeries, and their bioresorption after a recovery period eliminates the need for surgical extraction. Demonstrations in small and large animal models illustrate capabilities in monitoring leakage from the small intestine, the stomach, and the pancreas.
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Implantes Absorbibles , Fuga Anastomótica , Tracto Gastrointestinal , Ultrasonido , Animales , Humanos , Homeostasis , Estómago , Tracto Gastrointestinal/cirugía , Fuga Anastomótica/diagnóstico por imagen , Modelos AnimalesRESUMEN
The Pauson-Khand reaction has in the past 50 years become one of the most common cycloaddition reactions in chemistry. Coupling two unsaturated bonds with carbon monoxide, the transformation remains limited to CO as a C1 building block. Herein we report analogous cycloaddition reactions with nitrenes as an N1 unit. The reaction of a nonconjugated diene with a nitrene precursor produces bicyclic bioisosteres of common saturated heterocycles such as piperidine, morpholine, and piperazine. Experimental and computational mechanistic studies support relaying of the diradical nature of triplet nitrene into the π-system. We showcase the reaction's utility in late-stage functionalization of drug compounds and discovery of soluble epoxide hydrolase inhibitors.
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OBJECTIVES: To outline 44 major infectious diseases in the post-SARS (severe acute respiratory syndrome) in China and describe their long-term trends and changes by age, sex, epidemic season, and province. BACKGROUND: After the outbreak of severe acute respiratory syndrome (SARS) in 2003, with the change of infectious disease prevention and control system and the improvement of residents' quality of life, the incidence and mortality of infectious diseases have undergone major changes. METHODS: The data of 44 major infectious diseases in China from 2004 to 2018 were obtained from the monthly analysis report of the China Information System for Disease Control and Prevention (CISDCP) and the Public Health Science Data Center. Joinpoint r regression models were used to examine trends in incidence and mortality for 44 major and important infectious diseases from 2004 to 2018. RESULTS: From 2004 to 2018, 20,105, 500, 772 patients (10, 306, 546, 523 males and 9, 798, 954, 249 females) were diagnosed with 44 major infectious diseases. The overall incidence of 44 infectious diseases increased significantly from 294.6 per 100,000 people in 2004 to 479.1 per 100,000 people in 2010, with 7.9% APC (95% CI 5.2% -10.7%, P < 0.001), then slowed, and then increased to 561.2 per 100,000 people in 2018, with 1.5% APC (-0.1%-3.2%, P = 0.070). The overall mortality rose significantly, from 0.49 to 1.13 per 100,000 people between 2004 and 2011, with an APC increase of 11.6% (7.7% -15.6%, P < 0.001), and then remained stable until 2018. Among these, the prevalence of vaccine-preventable diseases and gastrointestinal & enteroviral diseases remained high and increased year by year. Patients with zoonotic diseases have the greatest risk of death, while patients with sexually transmitted and blood-borne diseases have the greatest number of deaths. Incidence rates vary considerably across geographic regions. Western China has a disproportionate burden of infectious diseases compared with eastern regions. CONCLUSIONS: After the event of SARS in 2003, infectious disease preventing and controlling model has undergone major changes in China, and certain achievements have been made in this field. Although overall morbidity and case fatality rates are still rising, they have leveled off. In reducing the disproportionate disease burden in the western region, expanding vaccination programs, preventing further increases in rates of sexually transmitted diseases, renewing efforts for emerging and persistent infectious diseases, and addressing seasonal and unpredictable outbreaks (such as the COVID-19 pandemic), there are still remain many challenges.
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Enfermedades Transmisibles , Pandemias , Masculino , Femenino , Humanos , Calidad de Vida , Enfermedades Transmisibles/epidemiología , Morbilidad , Incidencia , China/epidemiologíaRESUMEN
BACKGROUND: The increasing number of pertussis cases worldwide over the past two decades has challenged healthcare workers, and the role of environmental factors and climate change cannot be ignored. The incidence of pertussis has increased dramatically in mainland China since 2015, developing into a serious public health problem. The association of meteorological factors on pertussis has attracted attention, but few studies have examined the impact of air pollutants on this respiratory disease. METHODS: In this study, we analyzed the relationship between outdoor air pollution and the pertussis incidence. The study period was from January 2013 to December 2018, and monthly air pollutant data and the monthly incidence of patients in 31 provinces of China were collected. Distributed lag nonlinear model (DLNM) analysis was used to estimate the associations between six air pollutants and monthly pertussis incidence in China. RESULTS: We found a correlation between elevated pertussis incidence and short-term high monthly CO2 and O3 exposure, with a 10 µg/m3 increase in NO2 and O3 being significantly associated with increased pertussis incidence, with RR values of 1.78 (95% CI: 1.29-2.46) and 1.51 (95% CI: 1.16-1.97) at a lag of 0 months, respectively. Moreover, PM2.5 and SO2 also played key roles in the risk of pertussis surged. These associations remain significant after adjusting for long-term trend, seasonality and collinearity. CONCLUSIONS: Overall, these data reinforce the evidence of a link between incidence and climate identified in regional and local studies. These findings also further support the hypothesis that air pollution is responsible for the global resurgence of pertussis. Based on this we suggest that public health workers should be encouraged to consider the risks of the environment when focusing on pertussis prevention and control.
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Contaminantes Atmosféricos , Contaminación del Aire , Tos Ferina , Humanos , Incidencia , Tos Ferina/epidemiología , Exposición a Riesgos Ambientales/efectos adversos , Exposición a Riesgos Ambientales/análisis , Contaminación del Aire/efectos adversos , Contaminación del Aire/análisis , Contaminantes Atmosféricos/efectos adversos , Contaminantes Atmosféricos/análisis , China/epidemiología , Material Particulado/efectos adversos , Material Particulado/análisis , Dióxido de NitrógenoRESUMEN
Production of food-related products using microorganisms in an environmentally friendly manner is a crucial solution to global food safety and environmental pollution issues. Traditional microbial modification methods rely on artificial selection or natural mutations, which require time for repeated screening and reproduction, leading to unstable results. Therefore, it is imperative to develop rapid, efficient, and precise microbial modification technologies. This review summarizes recent advances in the construction of gene editing and metabolic regulation toolkits based on the clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated proteins (CRISPR-Cas) systems and their applications in reconstructing food microorganism metabolic networks. The development and application of gene editing toolkits from single-site gene editing to multi-site and genome-scale gene editing was also introduced. Moreover, it presented a detailed introduction to CRISPR interference, CRISPR activation, and logic circuit toolkits for metabolic network regulation. Moreover, the current challenges and future prospects for developing CRISPR genetic toolkits were also discussed.
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Sistemas CRISPR-Cas , Edición Génica , Sistemas CRISPR-Cas/genética , Edición Génica/métodos , AlimentosRESUMEN
Widely used agricultural greenhouses are critical in the development of facility agriculture because of not only their huge capacity in food and vegetable supplies, but also their environmental and climatic effects. Therefore, it is important to obtain the spatial distribution of agricultural greenhouses for agricultural production, policy making, and even environmental protection. Remote sensing technologies have been widely used in greenhouse extraction mainly in small or local regions, while large-scale and high-resolution (~ 1-m) greenhouse extraction is still lacking. In this study, agricultural greenhouses in an important agricultural province (Shandong, China) are extracted by the combination of high-resolution remote sensing images from Google Earth and deep learning algorithm with high accuracy (94.04% for mean intersection over union over test set). The results demonstrated that the agricultural greenhouses cover an area of 1755.3 km2, accounting for 1.11% of the total province and 2.31% of total cultivated land. The spatial density map of agricultural greenhouses also suggested that the facility agriculture in Shandong has obviously regional aggregation characteristics, which is vulnerable in both environment and economy. The results of this study are useful and meaningful for future agriculture planning and environmental management.
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Aprendizaje Profundo , Tecnología de Sensores Remotos , Agricultura/métodos , Verduras , Conservación de los Recursos Naturales , ChinaRESUMEN
BACKGROUND: Chronic entrapment neuropathy results in a clinical syndrome ranging from mild pain to debilitating atrophy. There remains a lack of objective metrics that quantify nerve dysfunction and guide surgical decision-making. Mechanomyography (MMG) reflects mechanical motor activity after stimulation of neuromuscular tissue and may indicate underlying nerve dysfunction. OBJECTIVE: To evaluate the role of MMG as a surgical adjunct in treating chronic entrapment neuropathies. METHODS: Patients 18 years or older with cubital tunnel syndrome (n = 8) and common peroneal neuropathy (n = 15) were enrolled. Surgical decompression of entrapped nerves was performed with intraoperative MMG of the hypothenar and tibialis anterior muscles. MMG stimulus thresholds (MMG-st) were correlated with compound muscle action potential (CMAP), motor nerve conduction velocity, baseline functional status, and clinical outcomes. RESULTS: After nerve decompression, MMG-st significantly reduced, the mean reduction of 0.5 mA (95% CI: 0.3-0.7, P < .001). On bivariate analysis, MMG-st exhibited significant negative correlation with common peroneal nerve CMAP ( P < .05), but no association with ulnar nerve CMAP and motor nerve conduction velocity. On preoperative electrodiagnosis, 60% of nerves had axonal loss and 40% had conduction block. The MMG-st was higher in the nerves with axonal loss as compared with the nerves with conduction block. MMG-st was negatively correlated with preoperative hand strength (grip/pinch) and foot-dorsiflexion/toe-extension strength ( P < .05). At the final visit, MMG-st significantly correlated with pain, PROMIS-10 physical function, and Oswestry Disability Index ( P < .05). CONCLUSION: MMG-st may serve as a surgical adjunct indicating axonal integrity in chronic entrapment neuropathies which may aid in clinical decision-making and prognostication of functional outcomes.
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Síndrome del Túnel Cubital , Conducción Nerviosa , Humanos , Conducción Nerviosa/fisiología , Nervio Cubital/cirugía , Síndrome del Túnel Cubital/diagnóstico , Síndrome del Túnel Cubital/cirugía , Músculo Esquelético , DolorRESUMEN
The metabolic burden caused by terpenoid accumulation limits the development of highly efficient microbial cell factories, which can be circumvented using exporter-mediated product secretion. Although our previous study showed that the pleiotropic drug resistance exporter (PDR11) mediates the export of rubusoside in Saccharomyces cerevisiae, the underlying mechanism is still unclear. Herein, we used GROMACS software to simulate PDR11-mediated rubusoside recruitment and found six residues (D116, D167, Y168, P521, R663, and L1146) on PDR11 that are critical for this process. We also explored the exportation potential of PDR11 for 39 terpenoids by calculating their binding affinity using batch molecular docking. Then, we verified the accuracy of the predicted results by conducting experiments with squalene, lycopene, and ß-carotene as examples. We found that PDR11 can efficiently secrete terpenoids with binding affinities lower than -9.0 kcal/mol. Combining the computer-based prediction and experimental verification, we proved that binding affinity is a reliable parameter to screen exporter substrates and might potentially enable rapid screening of exporters for natural products in microbial cell factories.
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Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Transportadoras de Casetes de Unión a ATP/genética , Transportadoras de Casetes de Unión a ATP/metabolismo , Terpenos/metabolismo , Simulación del Acoplamiento Molecular , Adenosina Trifosfato/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismoRESUMEN
Bioprocess control and optimization are crucial for tapping the metabolic potential of microorganisms, and which have made great progress in the past decades. Combination of the current control and optimization technologies with the latest computer-based strategies will be a worth expecting way to improve bioprocess further. Recently, artificial intelligence (AI) emerged as a data-driven technique independent of the complex interactions used in mathematical models and has been gradually applied in bioprocess. In this review, firstly, AI-guided modeling approaches of bioprocess are discussed, which are widely applied to optimize critical process parameters (CPPs). Then, AI-assisted rapid detection and monitoring technologies employed in bioprocess are summarized. Next, control strategies according to the above two technologies in bioprocess are analyzed. Lastly, current research gaps and future perspectives on AI-guided optimization and control technologies are discussed. This review provides theoretical guidance for developing AI-guided bioprocess optimization and control technologies.
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Inteligencia Artificial , Modelos Teóricos , Predicción , Lagunas en las EvidenciasRESUMEN
BACKGROUND: Commercially available near infrared spectroscopy devices for continuous free flap tissue oxygenation (StO2) monitoring can only be used on flaps with a cutaneous component. Additionally, differences in skin quality and pigmentation may alter StO2 measurements. Here, we present a novel implantable heat convection probe that measures microvascular blood flow for peripheral monitoring of free flaps, and is not subject to the same issues that limit the clinical utility of near-infrared spectroscopy. METHODS: The intratissue microvascular flow-sensing device includes a resistive heater, 4 thermistors, a small battery, and a Bluetooth chip, which allows connection to a smart device. Convection of applied heat is measured and mathematically transformed into a measurement of blood flow velocity. This was tested alongside Vioptix T.Ox in a porcine rectus abdominis myocutaneous flap model of arterial and venous occlusion. After flap elevation, the thermal device was deployed intramuscularly, and the cutaneous T.Ox device was applied. Acland clamps were alternately applied to the flap artery and veins to achieve 15 minutes periods of flap ischemia and congestion with a 15 minutes intervening recovery period. In total, five devices were tested in three flaps in three separate pigs over 16 vaso-occlusive events. RESULTS: Flow measurements were responsive to both ischemia and congestion, and returned to baseline during recovery periods. Flow measurements corresponded closely with measured StO2. Cross-correlation at zero lag showed agreement between these two sensing modalities. Two novel devices tested simultaneously on the same flap showed only minor variations in flow measurements. CONCLUSION: This novel probe is capable of detecting changes in tissue microcirculatory blood flow. This device performed well in a swine model of flap ischemia and congestion, and shows promise as a potentially useful clinical tool. Future studies will investigate performance in fasciocutaneous flaps and characterize longevity of the device over a period of several days.
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Colgajos Tisulares Libres , Colgajo Miocutáneo , Porcinos , Animales , Microcirculación , Colgajos Tisulares Libres/irrigación sanguínea , Isquemia , Complicaciones Posoperatorias , ArteriasRESUMEN
Serial examination and direct measurement of intracompartmental pressure (ICP) are suboptimal strategies for the detection of acute compartment syndrome (CS) because they are operator-dependent and yield information that only indirectly reflects intracompartmental muscle perfusion. As a result, instances of unnecessary fasciotomy and unrecognized CS are relatively common. Recently, near-infrared spectroscopy (NIRS)-based systems for compartment monitoring have generated interest as an adjunct tool. Under ideal conditions, NIRS directly measures the oxygenation of intracompartmental muscle (StO2 ), thereby obviating the challenges of interpreting equivocal clinical examination or ICP data. Despite these potential advantages, existing NIRS sensors are plagued by technical difficulties that limit clinical utility. Most of these limitations relate to their transcutaneous design that makes them susceptible to both interference from intervening skin/subcutaneous tissue, underlying hematoma, and instability of the skin-sensor interface. Here, we present a flexible, wireless, Bluetooth-enabled, percutaneously introducible intramuscular NIRS device that directly and continuously measures the StO2 of intracompartmental muscle. Proof of concept for this device is demonstrated in a swine lower extremity balloon compression model of acute CS, wherein we simultaneously track muscle oxygenation, ICP, and compartment perfusion pressure (PP). The observed StO2 decreased with increasing ICP and decreasing PP and then recovered following pressure reduction. The mean change in StO2 as the PP was decreased from baseline to 30 mmHg was -7.6%. The mean difference between baseline and nadir StO2 was -17.4%. Cross-correlations (absolute value) describing the correspondence between StO2 and ICP were >0.73. This novel intramuscular NIRS device identifies decreased muscle perfusion in the setting of evolving CS.
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Síndromes Compartimentales , Espectroscopía Infrarroja Corta , Porcinos , Animales , Músculos , Síndromes Compartimentales/diagnósticoRESUMEN
Optimizing the metabolic pathways of microbial cell factories is essential for establishing viable biotechnological production processes. However, due to the limited understanding of the complex setup of cellular machinery, building efficient microbial cell factories remains tedious and time-consuming. Machine learning (ML), a powerful tool capable of identifying patterns within large datasets, has been used to analyze biological datasets generated using various high-throughput technologies to build data-driven models for complex bioprocesses. In addition, ML can also be integrated with Design-Build-Test-Learn to accelerate development. This review focuses on recent ML applications in genome-scale metabolic model construction, multistep pathway optimization, rate-limiting enzyme engineering, and gene regulatory element designing. In addition, we have discussed some limitations of these methods as well as potential solutions.
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Physically transient forms of electronics enable unique classes of technologies, ranging from biomedical implants that disappear through processes of bioresorption after serving a clinical need to internet-of-things devices that harmlessly dissolve into the environment following a relevant period of use. Here, we develop a sustainable manufacturing pathway, based on ultrafast pulsed laser ablation, that can support high-volume, cost-effective manipulation of a diverse collection of organic and inorganic materials, each designed to degrade by hydrolysis or enzymatic activity, into patterned, multi-layered architectures with high resolution and accurate overlay registration. The technology can operate in patterning, thinning and/or cutting modes with (ultra)thin eco/bioresorbable materials of different types of semiconductors, dielectrics, and conductors on flexible substrates. Component-level demonstrations span passive and active devices, including diodes and field-effect transistors. Patterning these devices into interconnected layouts yields functional systems, as illustrated in examples that range from wireless implants as monitors of neural and cardiac activity, to thermal probes of microvascular flow, and multi-electrode arrays for biopotential sensing. These advances create important processing options for eco/bioresorbable materials and associated electronic systems, with immediate applicability across nearly all types of bioelectronic studies.
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Implantes Absorbibles , Electrónica , Semiconductores , Electrodos , Rayos LáserRESUMEN
High-sugar diet causes health problems, many of which can be addressed with the use of sugar substitutes. Rubusoside and rebaudiosides are interesting molecules, considered the next generation of sugar substitutes due to their low-calorie, superior sweetness and organoleptic properties. However, their low abundance in nature makes the traditional plant extraction process neither economical nor environmental-friendly. Here we engineer baker's yeast Saccharomyces cerevisiae as a chassis for the de novo production of rubusoside and rebaudiosides. In this process, we identify multiple issues that limit the production, including rate-liming steps, product stress on cellular fitness and unbalanced metabolic networks. We carry out a systematic engineering strategy to solve these issues, which produces rubusoside and rebaudiosides at titers of 1368.6 mg/L and 132.7 mg/L, respectively. The rubusoside chassis strain here constructed paves the way towards a sustainable, large-scale fermentation-based manufacturing of diverse rebaudiosides.
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Diterpenos de Tipo Kaurano , Ingeniería Metabólica , Diterpenos de Tipo Kaurano/metabolismo , Glucósidos/metabolismo , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , EdulcorantesRESUMEN
Implantable devices capable of targeted and reversible blocking of peripheral nerve activity may provide alternatives to opioids for treating pain. Local cooling represents an attractive means for on-demand elimination of pain signals, but traditional technologies are limited by rigid, bulky form factors; imprecise cooling; and requirements for extraction surgeries. Here, we introduce soft, bioresorbable, microfluidic devices that enable delivery of focused, minimally invasive cooling power at arbitrary depths in living tissues with real-time temperature feedback control. Construction with water-soluble, biocompatible materials leads to dissolution and bioresorption as a mechanism to eliminate unnecessary device load and risk to the patient without additional surgeries. Multiweek in vivo trials demonstrate the ability to rapidly and precisely cool peripheral nerves to provide local, on-demand analgesia in rat models for neuropathic pain.