Oxygen-to-ammonium-nitrogen ratio as an indicator for oxygen supply management in microoxic bioanodic ammonium oxidation.

Microbial electrolysis cells (MECs) have been proven effective for oxidizing ammonium (NH4+), where the anode acts as an electron acceptor, reducing the energy input by substituting oxygen (O2). However, O2 has been proved to be essential for achieving high removal rates MECs. Thus, precise control of oxygen supply is crucial for optimizing treatment performance and minimizing energy consumption. Unlike previous studies focusing on dissolved oxygen (DO) levels, this study introduces the O2/NH4+-N ratio as a novel control parameter for balancing oxidation rates and the selectivity of NH4+ oxidation towards dinitrogen gas (N2) under limited oxygen condition. Our results demonstrated that the O2/NH4+-N ratio is a more relevant oxygen supply indicator compared to DO level. Oxygen served as a more favorable electron acceptor than the electrode, increasing NH4+ oxidation rates but also resulting in more oxidized products such as nitrate (NO3-). Additionally, nitrous oxide (N2O) and N2 production were higher with the electrode as the electron acceptor compared to oxygen alone. An O2/NH4+-N ratio of 0.5 was found to be optimal, achieving a balance between product selectivity for N2 (51.4 % ± 4.5 %) and oxidation rates (344.6 ± 14.7 mg-N/L*d), with the columbic efficiency of 30.7 % ± 2.0 %. Microbial community analysis revealed that nitrifiers and denitrifiers were the primary bacteria involved, with oxygen promoting the growth of nitrite-oxidizing bacteria, thus facilitating complete NH4+ oxidation to NO3-. Our study provides new insights and guidelines on the appropriate oxygen dosage, offering strategies into optimizing operational conditions for NH4+ removal using MECs.

Protein rational design and modification of erythrose reductase for the improvement of erythritol production in Yarrowia lipolytica.

Erythritol is a natural non-caloric sweetener, which is produced by fermentation and extensively applied in food, medicine and chemical industries. The final step of the erythritol synthesis pathway is involved in erythritol reductase, whose activity and NADPH-dependent become the limiting node of erythritol production efficiency. Herein, we implemented a strategy combining molecular docking and thermal stability screening to construct an ER mutant library. And we successfully obtained a double mutant ERK26N/V295M (ER*) whose catalytic activity was 1.48 times that of wild-type ER. Through structural analysis and MD analysis, we found that the catalytic pocket and the enzyme stability of ER* were both improved. We overexpressed ER* in the engineered strain ΔKU70 to obtain the strain YLE-1. YLE-1 can produce 39.47 g/L of erythritol within 144 h, representing a 35% increase compared to the unmodified strain, and a 10% increase compared to the strain overexpressing wild-type ER. Considering the essentiality of NADPH supply, we further co-expressed ER* with two genes from the oxidative phase of PPP, ZWF1 and GND1. This resulted in the construction of YLE-3, which exhibited a significant increase in production, producing 47.85 g/L of erythritol within 144 h, representing a 63.90% increase compared to the original chassis strain. The productivity and the yield of the engineered strain YLE-3 were 0.33 g/L/h and 0.48 g/g glycerol, respectively. This work provided an ER mutation with excellent performance, and also proved the importance of cofactors in the process of erythritol synthesis, which will promote the industrial production of erythritol by metabolic engineering of Y. lipolytica.

Benchmarking circularity in supply chains: A systematic literature review.

The challenges posed by unsustainable practices in today's economy underscore the urgent need for a transition toward a circular economy (CE) and a holistic supply chain (SC) perspective. Benchmarking plays a pivotal role in managing circular SCs, offering a metric to gauge progress. However, the lack of consensus on the optimal benchmarking approach hampers effective implementation of circular business practices. To address this gap, we conducted a systematic review of the literature, identifying 29 pertinent publications. The analysis revealed 30 unique attributes and sub-attributes for benchmarking circularity, which were clustered into five main attributes. The main attributes are goals, subjects, key performance indicators (KPIs), data sources, and evaluation methods, while the sub-attributes are organised as features of the main attributes and depicted as a feature model. Drawing from selected publications, we illustrated each feature with examples. Our model offers a comprehensive benchmarking reference for circularity and will be a valuable tool for managers in the transition toward circularity. Supply chains seeking to benchmark their transition to circularity can apply the reference model to ensure that their benchmarking strategy is consistent with state-of-the-art knowledge. By providing a generic circularity benchmarking approach that is valid for diverse economic sectors, our findings contribute to theoretical efforts to address the lack of generic frameworks for CE.

Dairy cow parity affects relationships among nutritional parameters in the blood of dams, umbilical cords, and calves and placental development at calving.

Heifer growth and milk production in lactating cows may diminish the nutrient supply to the fetus. This study aimed to analyze the characteristics of the nutrient supply to the fetus in primiparous and multiparous cows. We investigated maternal, umbilical cord, and calf blood glucose and amino acid levels, as well as placental development in 28 primiparous (PP) and 30 multiparous (MP) Holstein cows. Although the total cotyledonary weight and surface area showed no significant differences, the MP group exhibited larger individual cotyledons (P < 0.01) and fewer medium-sized cotyledons (P < 0.05). Within the PP group, total cotyledonary weight and surface area positively correlated with blood glucose (r = 0.71-0.77; P < 0.01) and total essential amino acid (r = 0.55; P < 0.05) concentrations in the umbilical veins. However, no significant correlation was observed in the MP group. Blood glucose and amino acid concentrations in the umbilical vein, umbilical artery, and calf were significantly lower in the MP group (P < 0.05), although no difference was observed in the dams between the groups. In conclusion, the nutrient status of primiparous cows can alter fetal nutrient supply. Moreover, multiparous cows have larger individual cotyledons as an adaptive response to increased milk production during pregnancy. However, this adaptive response in multiparous cows did not completely restore nutrient supply to the fetus to the same extent as that in primiparous cows. Therefore, the nutritional management of multiparous cows during pregnancy must be reconsidered.

How does the data element-driven industry affect corporate cash holdings? Evidence from Chinese listed companies.

The data element-driven industry (DEDI) generates large amounts of data, thereby mitigating information asymmetry. Does this affect corporate cash holdings? On the basis of theoretical analysis, this study empirically analyzes the impact of DEDI on enterprises' cash holdings and its transmission path using data of Chinese cities and A-share listed enterprises from 2008 to 2020. First, the results indicate that the DEDI reduces corporate cash holdings. As the development level of the DEDI improves, the corporate cash holdings gradually decrease. Second, the DEDI indirectly affects corporate cash holdings by influencing debt-financing and external credit supply capacities. Specifically, the DEDI increases the upstream corporate debt-financing and downstream corporate external credit supply capacities. Improvements in debt-financing and the external credit supply capacities can reduce corporate cash holdings. Third, the DEDI has a heterogeneous impact. For enterprise with CEO duality, small and medium-sized, and information technology enterprises, the impact of DEDI in reducing cash holdings is greater.

Rethinking counterfeit medical supply chains: A critical review of the current literature.

The medical device and pharmaceutical industries include a range of drugs, machines, instruments, and apparatuses used to prevent, diagnose, treat disease and illness, or aid in rehabilitation for patients, and are expected to grow substantially in the coming years. However, they are often targets of criminal organizations who manufacture and profit from fraudulent products, infiltrating the market with counterfeit medical supply chains. In this paper, we discuss and analyze the extent and nature of this problem and make suggestions for mitigation and prevention of this worldwide challenge. Ultimately, we argue that a holistic approach is essential to addressing this problem, including the creation and dissemination of reliable and good quality data, developing healthcare systems to be more robust, establishing/enhancing intra- and international cooperation around this issue, and employing effective technological solutions, such as digital tracing.

Convergent technologies to tackle challenges of modern food authentication.

The authentication process involves all the supply chain stakeholders, and it is also adopted to verify food quality and safety. Food authentication tools are an essential part of traceability systems as they provide information on the credibility of origin, species/variety identity, geographical provenance, production entity. Moreover, these systems are useful to evaluate the effect of transformation processes, conservation strategies and the reliability of packaging and distribution flows on food quality and safety. In this manuscript, we identified the innovative characteristics of food authentication systems to respond to market challenges, such as the simplification, the high sensitivity, and the non-destructive ability during authentication procedures. We also discussed the potential of the current identification systems based on molecular markers (chemical, biochemical, genetic) and the effectiveness of new technologies with reference to the miniaturized systems offered by nanotechnologies, and computer vision systems linked to artificial intelligence processes. This overview emphasizes the importance of convergent technologies in food authentication, to support molecular markers with the technological innovation offered by emerging technologies derived from biotechnologies and informatics. The potential of these strategies was evaluated on real examples of high-value food products. Technological innovation can therefore strengthen the system of molecular markers to meet the current market needs; however, food production processes are in profound evolution. The food 3D-printing and the introduction of new raw materials open new challenges for food authentication and this will require both an update of the current regulatory framework, as well as the development and adoption of new analytical systems.

Recycling channel strategy in the presence of free-riding in the carbon neutrality era.

Recycling has become a critical response to the goals of reaching a carbon peak and achieving carbon neutrality. This study explores the effects of consumer free-riding behavior, the quality of recycling services, and the costs of channel transfers on the profitability of manufacturers and retailers in a dual-channel closed-loop supply chain (CLSC), focusing on the importance of recycling practices for carbon neutrality. Using consumer utility theory and a Stackelberg game model, we analyze the dynamics among these factors. Our results show that: (i) Consumer free-riding behavior slightly increases market demand and recycling volumes, enhancing profitability for both manufacturers and retailers in the dual-channel CLSC. (ii) The quality of recycling services and the transfer costs associated with retailer free-riding behavior jointly influence the profits of manufacturers and retailers. (iii) The effect of free-riding behavior on recycling services affects both forward sales and reverse recycling channels equally. This study provides valuable insights for decision-making in sustainable development practices in the recycling sector, significantly contributing to the goal of achieving carbon neutrality.

NIR-II AIE Luminogen-Based Erythrocyte-Like Nanoparticles with Granuloma-Targeting and Self-Oxygenation Characteristics for Combined Phototherapy of Tuberculosis.

Tuberculosis, a fatal infectious disease caused by Mycobacterium tuberculosis (M.tb), is difficult to treat with antibiotics due to drug resistance and short drug half-life. Phototherapy represents a promising alternative to antibiotics in combating M.tb. Exploring an intelligent material allowing effective tuberculosis treatment is definitely appealing, yet a significantly challenging task. Herein, an all-in-one biomimetic therapeutic nanoparticle featured by aggregation-induced second near-infrared emission, granuloma-targeting, and self-oxygenation is constructed, which can serve for prominent fluorescence imaging-navigated combined phototherapy toward tuberculosis. After camouflaging the biomimetic erythrocyte membrane, the nanoparticles show significantly prolonged blood circulation and increased selective accumulation in tuberculosis granuloma. Upon laser irradiation, the loading photosensitizer of aggregation-induced emission photosensitizer elevates the production of reactive oxygen species (ROS), causing M.tb damage and death. The delivery of oxygen to relieve the hypoxic granuloma microenvironment supports ROS generation during photodynamic therapy. Meanwhile, the photothermal agent, Prussian blue nanoparticles, plays the role of good photothermal killing effect on M.tb. Moreover, the growth and proliferation of granuloma and M.tb colonies are effectively inhibited in the nanoparticle-treated tuberculous granuloma model mice, suggesting the combined therapeutic effects of enhancing photodynamic therapy and photothermal therapy.

A method to describe attenuation of river contamination under peak flows: Can the public water supply from Paraopeba River finally return after the Brumadinho dam disaster?

Tailings dams' disasters begin a stage of river water contamination with no endpoint at first sight. But when the river was formerly used for public water supply and the use was suspended as consequence of a dam break, a time window for safe suspension lift must be anticipated to help water managers. The purpose of this study was to seek for that moment in the case of Brumadinho dam disaster which occurred in 2019 and injected millions of cubic meters of iron- and manganese-rich tailings into the Paraopeba River, leading to the suspension of public water supply to Belo Horizonte metropolitan region with this resource, until now. To accomplish the proposed goal, an assemblage of artificial intelligence and socio-economic development models were used to anticipate precipitation, river discharge and metal concentrations (iron, manganese) until 2033. Then, the ratios of metal concentrations between impacted and non-impacted sites were determined and values representing extreme events of river discharge were selected for further assessment. A ratio ≈1 generally indicates a similarity between impacted and non-impacted areas or, put another way, a return of impacted areas to a pre-rupture condition. Moreover, when the ratio is estimated under the influence of peak flows, then a value of ≈1 indicates a return to pre-rupture conditions under the most unfavorable hydrologic regimes, thus a safe return. So, the extreme ratios were plotted against time and fitted to a straight line with intercept-x representing the requested safe time. The results pointed to 6.57 years after the accident, while using iron as contaminant indicator, or 8.71 years when manganese was considered. Despite of being a relatively low-risk timeframe, the suspension lift should be implemented in phases and monitored for precaution of potential sporadic contamination events, while dredging of the tailings from impacted areas should continue and be accelerated.

Three-dimensional dynamic homogenous modeling: The biomechanical influences of leg tissue stiffness on pressure performance of compression biomedical therapeutic textiles.

Patient compliance and therapeutic precision of compression textiles (CTs) are frequently limited by the inaccurate pressure distributions along biological bodies in physical-based compression therapy. Therefore, the biomechanical influences of physiological tissue material characteristics of lower extremities on compression generations of CTs need to be explored systematically to improve pressure management efficacy. In this study, we developed three-dimensional (3D) homogenous finite element (FE) CT-leg systems to qualitatively compare the pressure diversities along lower limbs with different biomaterial tissue properties under each external compression level. Simultaneously, through the obtained leg circumferential displacement, a contact analysis model was applied to quantitatively explore the impact mechanisms of soft leg indentations on the pressure performance of CTs. Based on the experimental validation study, the proposed FE systems could be efficiently utilized for compression performance prediction (error ratio: 7.45%). Through the biomechanical simulation and theoretical calculations, the tissue stiffness characteristics of applied bodies showed significant correlations (p < 0.05) with the body circumferential displacements but no correlations (p > 0.05) with pressure delivery differences of CTs. This study facilitates the pressure fit design principle and leg mannequin material selection guidance for the development and experimental assessment of CTs. It also provides effective simulation methods for pressure prediction and property parametric optimization of compression materials.

A comparative analysis of NADPH supply strategies in Saccharomyces cerevisiae: Production of d-xylitol from d-xylose as a case study.

Enhancing the supply of the redox cofactor NADPH in metabolically engineered cells is a critical target for optimizing the synthesis of many product classes, such as fatty acids or terpenoids. In S. cerevisiae, several successful approaches have been developed in different experimental contexts. However, their systematic comparison has not been reported. Here, we established the reduction of xylose to xylitol by an NADPH-dependent xylose reductase as a model reaction to compare the efficacy of different NADPH supply strategies in the course of a batch fermentation, in which glucose and ethanol are sequentially used as carbon sources and redox donors. We show that strains overexpressing the glucose-6-phosphate dehydrogenase Zwf1 perform best, producing up to 16.9 g L-1 xylitol from 20 g L-1 xylose in stirred tank bioreactors. The beneficial effect of increased Zwf1 activity is especially pronounced during the ethanol consumption phase. The same notion applies to the deletion of the aldehyde dehydrogenase ALD6 gene, albeit at a quantitatively lower level. Reduced expression of the phosphoglucose isomerase Pgi1 and heterologous expression of the NADP+-dependent glyceraldehyde-3-phosphate dehydrogenase Gdp1 from Kluyveromyces lactis acted synergistically with ZWF1 overexpression in the presence of glucose, but had a detrimental effect after the diauxic shift. Expression of the mitochondrial NADH kinase Pos5 in the cytosol likewise improved the production of xylitol only on glucose, but not in combination with enhanced Zwf1 activity. To demonstrate the generalizability of our observations, we show that the most promising strategies - ZWF1 overexpression and deletion of ALD6 - also improve the production of l-galactonate from d-galacturonic acid. Therefore, we expect that these findings will provide valuable guidelines for engineering not only the production of xylitol but also of diverse other pathways that require NADPH.

Analyzing resilience influencing factors in the prefabricated building supply chain based on SEM-SD methodology.

The supply chain for prefabricated buildings (PB) currently grapples with pressing challenges. In order to ensure the safe and stable development of the prefabricated building supply chains (PBSC), this study aims to identify the key factors and internal mechanisms affecting the PBSC, and propose a supply chain resilience enhancement mechanism, so as to promote the sustainable development of the PB industry. The study combined a literature review and survey data to identify key resilience factors in PBSC. A Structural Equation Model (SEM) was used to explore the relationships between these factors. System dynamics were applied to create a simulation model, assessing the resilience impact level and conducting sensitivity analysis. The results show that the transportation and procurement processes are the most significant factors influencing supply chain resilience. The external environmental factors wielded a more pronounced impact on the overall evaluation of supply chain resilience than the delivery and use processes, but delivery and use processes are more sensitive. The study uses the Pressure-State-Response (PSR) model to suggest strategies for enhancing supply chain resilience. This study contributes to more sustainable and efficient construction practices by offering an innovative theoretical framework to analyze the factors influencing PBSC resilience and proposing enhancement strategies.

Emergency preparedness in the central sterile supply department: a multicenter cross-sectional survey.

OBJECTIVE: To investigate the current situation of emergency preparation and emergency drill in the CSSD, and analyze its influence on the nurses' emergency attitude and ability. METHODS: This study employed a multicenter stratified sampling method, conducted from January to June 2023 using the online survey, participants completed the general data, emergency preparedness and drill questionnaire, public health emergency response questionnaire and emergency capacity scale. An independent samples t test or Kruskal-Wallis test was used to analyse differences in nurses' emergency capacity and attitudes. RESULTS: The data from 15 provinces 55 hospitals in China. Overall, 77.58% of participants' institutions set up emergency management teams, 85.45% have an emergency plan and revise it regularly. 92.12% store emergency supplies. All survey staff participated in the emergency drill, which predominantly consisted of individual drills (51.52%), with 90.30% being real combat drills, 49.09% of participants engaging in drills every quarter, and 91.52% of the drill's participants exceeding 50%. The respondents' emergency attitude score was (29.346 ± 6.029), their emergency ability score was (63.594 ± 10.413), and those with rescue experience showed a more positive attitude (Z = -2.316, P = 0.021). Different titles, education levels, rescue experience and the frequency of emergency drill affected the emergency rescue ability of the respondents (P < 0.05). CONCLUSIONS: Most medical institutions establish emergency management systems and plans, yet the content lacks geographical specificity.The duration and participation of emergency drills are high, but the effectiveness of the drills needs to be further improved, and the response capacity and attitudes of CSSD nurses are low. It is recommended that agencies develop comprehensive and targeted contingency plans to strengthen the inspection and evaluation of team strength, equipment and safeguards against the contingency plans, so as to ensure that the measures mandated by the contingency plans can be implemented promptly after the emergency response is initiated.

The Sustainability Journey of Chinese Ready-Meal Companies Going Global: Configurational Analysis Using the Technology-Organization-Environment Framework.

In the new wave of globalization, China's pre-cooked meal industry has rapidly emerged as a significant player in the food supply chain domain, owing to its convenience and diverse choices. Amidst intensifying market competition, crafting a sustainable supply chain for overseas expansion has become an indispensable core element for driving corporate internationalization. This study focuses on the sustainability generation mechanism of the overseas supply chain of Chinese pre-cooked meal A-share listed companies, employing the technology-organization-environment (TOE) framework and fuzzy-set qualitative comparative analysis (fsQCA) method. Herein, an in-depth analysis of 388 data points from 17 listed companies has been conducted. The study systematically reveals the key factors affecting the sustainability of overseas supply chains and identifies three critical sustainability generation paths: the technology-driven and norm compliance model (path 1), the market sensitivity and product innovation model (path 2), and the robust operation and risk control model (path 3). The present study not only introduces a novel perspective on the application of a TOE framework within the realms of sustainable supply chain management and environmental, social, and governance (ESG) criteria but also offers clear directions for companies to enhance sustainability in their overseas expansion process. This includes strengthening technological research and development, compliance construction, market adaptability, product diversity, infrastructure construction, and risk management. Moreover, the research findings provide valuable insights for policymakers in promoting the internationalization of the pre-cooked meal industry and enhancing industry competitiveness.

Personalized compression therapeutic textiles: digital design, development, and biomechanical evaluation.

Physical-based external compression medical modalities could provide sustainable interfacial pressure dosages for daily healthcare prophylaxis and clinic treatment of chronic venous disease (CVD). However, conventional ready-made compression therapeutic textiles (CTs) with improper morphologies and ill-fitting of pressure exertions frequently limit patient compliance in practical application. Therefore, the present study fabricated the personalized CTs for various subjects through the proposed comprehensive manufacturing system. The individual geometric dimensions and morphologic profiles of lower extremities were characterized according to three-dimensional (3D) body scanning and reverse engineering technologies. Through body anthropometric analysis and pressure optimization, the knitting yarn and machinery variables were determined as the digital design strategies for 3D seamless fabrication of CTs. Next, to visually simulate the generated pressure mappings of developed CTs, the subject-specific 3D finite element (FE) CT-leg modelings with high accuracy and acceptability (pressure prediction error ratio: 11.00% ± 7.78%) were established based on the constructed lower limb models and determined tissue stiffness. Moreover, through the actual in vivo trials, the prepared customized CTs efficiently (Sig. <0.05; ρ = 0.97) distributed the expected pressure requirements referring to the prescribed compression magnitudes (pressure error ratio: 10.08% ± 7.75%). Furthermore, the movement abilities and comfortable perceptions were evaluated subjectively for the ergonomic wearing comfort (EWC) assessments. Thus, this study promotes the precise pressure management and clinical efficacy for targeted users and leads an operable development approach for related medical biomaterials in compression therapy.

Multi-scale assessment of rainwater harvesting availability across the continental U.S.

Addressing resilience, sustainability, and water resource conservation has become increasingly important in the modern world. Challenges arise due to periodic droughts, climate change, and seasonal variability in areas with limited freshwater availability. Therefore, implementing and promoting water reuse is essential. Rainwater harvesting (RWH) is one such alternative, offering benefits in conserving water resources and mitigating droughts while reducing urban flooding and costs by generating alternative lower-cost water sources. Providing users with knowledge of available volumes for harvesting, including homeowners and governmental entities, is key to encouraging this practice. Hydrological data and geographic information systems are fundamental for managing, designing, and projecting rainwater harvesting practices. However, no tools currently integrate this information at multiple scales with current and future climate scenarios. This research aimed to develop a multi-scale assessment tool named H2O HARVEST, for evaluating the availability and potential of rainwater harvesting. Additional benefits of the H2O HARVEST app include aiding decision-making by national governmental entities and analyzing potential future scenarios for homeowner users. The app also provides regulatory policy information at the state level. We offer an app with the necessary capabilities to bridge the technology gap and promote rainwater harvesting practices. Our research demonstrated that RWH has the potential to be a sustainable water reuse practice. For more than 50% of the states, the RWH could supply at least 50% of the water demand. The regions of the US with the greatest potential are the Central and East.

Using Novel Multimethod Evaluation Approaches to Understand Complex Food System Interventions: Insights from a Supply Chain Intervention Intended to Improve Nutrition.

Background: A "food system" approach to improve diet quality by intervening within areas such as food supply chains is gaining prominence. However, evidence of such interventions' impact, and understanding of appropriate methods to evaluate them, is lacking. Objectives: We present an impact evaluation of an intervention that aimed to increase consumption of nutritious foods by supporting food-producing firms in Kenya. In doing so, we demonstrate how multiple methods, including those from other disciplines, can be used to evaluate a complex food systems intervention. Methods: Four methods focused on food-producing firms and their management, including a survey of intervention participants (n = 83 individuals), a "laboratory-in-the-field" experiment (n = 83 individuals), baseline/endline data on firm performance (n = 71 firms), and semistructured interviews (n = 19 firms). Three methods focused on consumers in neighborhoods targeted by a supported firm: a randomized field experiment tested effects of making a supported product exhaustively available on consumers' purchases and consumption (n = 1295 consumers); 3 discrete choice experiments (n = 1295 consumers) tested factors influencing consumers' willingness to pay for foods with relevant characteristics. Results: Among firms, we saw suggestive evidence of increased networking and business relationships, while laboratory-in-the-field experiments indicated the intervention might foster cooperation among participants. Qualitative interviews suggested that the intervention enabled firms to increase production, improve management, increase revenues, and lower costs. Baseline/endline data confirmed a positive effect only on the launch of new products and hiring workers. In the field experiment, consumption of the supported product increased in areas where it was made available relative to a control group, but this did not increase overall consumption of the food type or dietary diversity. Conclusions: Results showed positive signs of the intervention improving firm-level outcomes but limited impact on consumers' diet quality. The evaluation also demonstrates how diverse methods can be used to evaluate complex interventions.

Modular Prodrug-Engineered Oxygen Nano-Tank With Outstanding Nanoassembly Performance, High Oxygen Loading, and Closed-Loop Tumor Hypoxia Relief.

The clinical translation of tumor hypoxia intervention modalities still falls short of expectation, restricted by poor biocompatibility of oxygen-carrying materials, unsatisfactory oxygen loading performance, and abnormally high cellular oxygen consumption-caused insufficient hypoxia relief. Herein, a carrier-free oxygen nano-tank based on modular fluorination prodrug design and co-assembly nanotechnology is elaborately exploited, which is facilely fabricated through the molecular nanoassembly of a fluorinated prodrug (FSSP) of pyropheophorbide a (PPa) and an oxygen consumption inhibitor (atovaquone, ATO). The nano-tank adeptly achieves sufficient oxygen enrichment while simultaneously suppressing oxygen consumption within tumors for complete tumor hypoxia alleviation. Significant, the fluorination module in FSSP not only confers favorable co-assemblage of FSSP and ATO, but also empowers the nanoassembly to readily carry oxygen. As expected, it displays excellent oxygen carrying capacity, favorable pharmacokinetics, on-demand laser-triggerable ATO release, closed-loop tumor hypoxia relief, and significant enhancement to PPa-mediated PDT in vitro and in vivo. This study provides a novel nanotherapeutic paradigm for tumor hypoxia intervention-enhanced cancer therapy.

Gas supply apparatus using rotational motion of shaking incubator for flask culture of aerobic microorganisms.

Shake flask cultivation, a cornerstone in bioprocess research encounters limitations in supplying sufficient oxygen and exchanging gases, restricting its accuracy in assessing microbial growth and metabolic activity. In this communication, we introduce an innovative gas supply apparatus that harnesses the rotational motion of a shaking incubator to facilitate continuous air delivery, effectively overcoming these limitations. We measured the mass transfer coefficient (kLa) and conducted batch cultures of Corynebacterium glutamicum H36LsGAD using various working volumes to assess its performance. Results demonstrated that the gas supply apparatus significantly outperforms conventional silicone stoppers regarding oxygen delivery, with kLa values of 2531.7 h-1 compared to 20.25 h-1 at 230 rpm. Moreover, in batch cultures, the gas supply apparatus enabled substantial improvements in microbial growth, maintaining exponential growth even at larger working volumes. Compared to the existing system, an increase in final cell mass by a factor of 3.4-fold was observed when utilizing 20% of the flask's volume, and a remarkable 9-fold increase was achieved when using 60%. Furthermore, the gas supply apparatus ensured consistent oxygen supply and efficient gas exchange within the flask, overcoming challenges associated with low working volumes. This approach offers a simple yet effective solution to enhance gas transfer in shake flask cultivation, bridging the gap between laboratory-scale experiments and industrial fermenters. Its broad applicability holds promise for advancing research in bioprocess optimization and scale-up endeavors.