The clinical success of chimeric antigen receptor (CAR) T-cell therapies has revolutionized oncology, yet the high costs and logistical complexities of ex vivo manufacturing remain significant barriers to global patient access. In vivo cell therapy, which involves the direct injection of lentiviral vectors (LVVs) to engineer cells within the patient’s body, offers a promising, cost-effective alternative. However, transitioning from ex vivo to in vivo applications necessitates a fundamental shift in LVV biomanufacturing to ensure safety and efficacy. This paper examines the critical bottlenecks in the current LVV production landscape. In upstream processing, we explore LVV particle assembly and maturation mechanisms, the effect of transgene size on LVV functional titers and the formation of non-functional byproducts, including empty and partially formed LVV particles and extracellular vesicles (EVs). These impurities pose severe risks of immunotoxicity and insertional mutagenesis when delivered in vivo. In downstream processing, we highlight the challenges of purifying labile LVV particles, emphasizing the need for rapid, high-resolution separation techniques like continuous processing to maintain functional titers. Furthermore, we address the limitations of current analytical assays, which often fail to distinguish mature, functional LVVs from structurally similar but inactive contaminants. We conclude that the future of in vivo lentiviral therapy depends on developing novel purification strategies based on subtle biophysical differences—such as surface charge and capsid morphology—and implementing robust, high-throughput analytics to ensure delivery of high-purity, potent therapeutic viral vectors.

Reimagining oil recovery: Sustainable downstream processing of oleaginous yeasts for food applications.

Organizations increasingly face mounting pressure to improve operational efficiency while simultaneously pursuing long-term business sustainability amid volatile markets, supply chain disruptions, and growing environmental and social accountability. Despite this urgency, workflow optimization initiatives are frequently implemented independently of supply chain optimization efforts, resulting in fragmented decision-making, misaligned performance metrics, and suboptimal sustainability outcomes. This study examines how the strategic integration of workflow and supply chain optimization can enhance operational performance, supply chain resilience, and sustainability outcomes in a real-world organizational context. Using an in-depth case study of a mid-sized manufacturing organization, this research analyzes the firm’s transition from functionally siloed operational improvements to a coordinated, end-to-end optimization approach. Data was collected through semi-structured interviews with key stakeholders across operations and supply chain functions, analysis of internal operational and supply chain performance records, and review of sustainability and environmental impact reports. A triangulated analysis was employed to assess changes in performance before and after integration. The findings reveal that aligning internal workflows with upstream and downstream supply chain processes led to significant reductions in cycle time and process variability, improved inventory turnover and service levels, and stronger supplier collaboration and coordination. Importantly, these operational and supply chain improvements were accompanied by measurable sustainability benefits, including reduced material waste, lower energy consumption, and decreased transportation-related emissions. The results suggest that sustainability gains were not incidental but rather emerged as a direct outcome of integrated decision-making and aligned performance incentives. This study contributes to the operations and supply chain management literature by providing empirical evidence on the role of workflow supply chain integration in achieving sustainable performance improvements. It extends existing research by demonstrating how integration of mechanisms, governance structures, and shared metrics can translate efficiency gains into long-term sustainability outcomes. From a practical perspective, the study offers a structured framework and actionable insights for managers seeking to move beyond isolated optimization initiatives toward integrated, sustainability-driven operational strategies.

Abstract It remains uncertain whether precipitation oxygen isotopes (δ 18 O) reliably capture East Asian Meiyu monsoon variability. Analyzing daily δ 18 O across the Yangtze-Huai River Basin from 28-34°N, we reveal a distinct spatial dichotomy. In the middle and northern Meiyu regions, δ 18 O robustly tracks Meiyu precipitation. Conversely, the southern Meiyu margin is decoupled from Meiyu variability, primarily reflecting upstream convection processes further south. We identify the western Pacific subtropical high (WPSH) as the central driver, creating a dynamic dipole: its northwestward extension enhances moisture transport and deep convection along its northwestern flank (driving isotopic depletion in the northern Meiyu region), while imposing subsidence and convective inhibition under its body (suppressing isotopic depletion in the southern Meiyu region). Importantly, these mechanisms persist on interannual timescales. Consequently, while northern δ 18 O records effectively capture Meiyu variability, southern records reflect distinct vertical constraints, necessitating spatially differentiated paleoclimate interpretations.

Lignin upgrading for sustainable materials and chemicals: From waste to functional bioplastics.

Wave bioreactors are commonly used in biopharmaceutical upstream processes as an intermediate stage between shake flasks and stirred tanks within the seed train. They offer a controlled environment for cell cultivation while minimizing shear stress. Accurate characterization of these systems is essential for optimizing cell culture performance, particularly as state of the art cell lines require higher volumetric mass transfer coefficients k L a. This study aims to determine the volumetric mass transfer coefficient through experiments and computational fluid dynamics (CFD) simulations. An improved experimental method for the measurements of the volumetric mass transfer is presented, with results correlated to key process parameters: rocking angle, rocking rate, and filling volume. In addition, CFD simulations were caried out using M-Star CFD by means of a Lattice-Boltzmann Method-based solver. The mass transfer was calculated using Higbie's penetration theory, incorporating the Kolmogorov scale to define contact time. The analysis also integrates concepts from Friedl and the surface renewal model, introducing the surface normal velocity as an additional parameter in the mass transfer coefficient k L calculation. Analyzes were carried out for 10 and 50L wave bioreactors, with one degree of freedom movement. Optimized process parameters were identified and validated in biological cultivations, resulting in increased dissolved oxygen levels in the medium. These findings contribute to improved characterization and control of wave bioreactors, enabling more accurate prediction of process parameter effects.

Shake flasks are widely used in early-stage bioprocess development but are limited by their inability to monitor and control key gas-transfer variables such as dissolved oxygen and carbon dioxide. In this study, we present a jacketed breathable flask system that enables real-time gas control in a standard shaking environment. Across multiple media formulations and fill volumes, this system consistently deferred oxygen limitation and enhanced culture performance, achieving > 150% higher biomass and 140% greater recombinant protein yield compared to conventional flasks. Time-resolved analysis of pH and extracellular metabolites revealed reduced accumulation of oxygen-sensitive byproducts, including acetate, pyruvate, and succinate, indicating a shift toward more efficient respiratory metabolism. The jacketed breathable flask also enabled continuous monitoring and regulation of critical process parameters, creating a bioreactor-like environment in a high-throughput, low-cost format. The biomass accumulation and specific growth rate observed in jacketed breathable flask are comparable to those reported for Escherichia coli cultures in stirred tank bioreactor application notes for Eppendorf BioBLU 3f. These findings establish breathable flasks as a scalable and accessible platform with bioreactor-like performance for upstream process optimization and accelerate biomanufacturing development at the lab scale.

ABSTRACT Microalgae are cell factories rich in biochemicals that can be used as a feedstock for applications such as medicines, nutraceuticals, food, feed and bioenergy. Developing economical and efficient cultivation media is a major challenge in microalgal biomass production, as efficient upstream cultivation processes are crucial for continuous biomass resource supply. Nano-based fertilisers are being developed and currently used in agricultural cultivation for greater efficacy compared to conventional chemical fertilisers. Use of nanotechnology in microalgal biotechnology is in its infancy, and use of nano-based media for microalgal cultivation is yet to be explored. In this study, a novel nano-based cultivation medium named nano-JAPH medium was formulated and standardized. The efficacy of nano-JAPH medium was tested at different nutrient concentrations and validated through laboratory-scale trials with the microalgae, Chlorella vulgaris, Chlorococcum humicola, Oocystis crassa, Scenedesmus quadricauda and Synechococcus aeruginosus. The pilot-scale outdoor trials using nano-JAPH medium were carried out subsequently with Chlorella vulgaris in a suspended cultivation system and with a polyculture microalgal consortium in an immobilized cultivation system against modified NMR commercial medium as control. The results showed that nano-JAPH medium resulted in significantly higher areal biomass productivity (10.545 g m‒2 d‒1 in suspended and 2.9 g m‒2 d‒1 in attached systems) compared to those in control with 42.3% and 13.2% increase, respectively. This study shows that the novel nano-JAPH medium can be effectively used to increase microalgae biomass productivity and facilitate commercial microalgae mass culture through sustained supply of nutrients.

Monoclonal antibodies (mAbs) are nowadays fundamental in treating a wide range of severe diseases, including cancer, infections, or autoimmune disorders. Due to their high specificity, potent activity, and fewer side effects compared to small molecular drugs, the market for mAbs is growing continuously. Consequently, there is an increasing demand for process intensification technologies to increase the mAb throughput. This study introduces a novel integrated continuous biomanufacturing (ICB) process at lab-scale as a tool for process development. The ICB comprises a perfusion cultivation as an upstream process (USP) as well as a continuous multi-column chromatography capture step using membrane adsorbers (RC-BioSMB) and a continuous virus inactivation (VI) approach for the subsequent downstream processing. The process was continuously operated for 4 days. USP variations, like changes in titer and permeate flow rate, were successfully addressed by an adaptive control of the flow rates through all unit operations. The small-scale ICB was used to establish an adaptive control of the RC-BioSMB loading volume. A novel approach for the subsequent continuous VI was developed to enable processing at lab-scale with the associated very low flow rates. Throughout the lab-scale ICB process, a high overall yield of 88% was obtained with simultaneous high removal of process-related impurities like host cell proteins (3.4 log removal to 73 ppm) and DNA (2.9 log removal to 0.8 ppm).

Accurate reconstruction of Respiratory Virus Transmission Networks (RVTNs) depends heavily on the reliability of RT-PCR results, which are directly influenced by upstream RNA extraction processes. This study evaluates three commonly used extraction methods silica column, magnetic bead–based, and rapid lysis to determine their impact on RT-PCR sensitivity, Ct variability, viral load estimation, and downstream RVTN model stability. Experimental analyses showed that magnetic bead extraction consistently produced the highest RNA yield, lowest Ct variability, and most stable amplification performance, resulting in minimal propagation error within transmission modeling. Silica column extraction demonstrated moderate reliability, while rapid lysis produced substantial Ct variability and high diagnostic uncertainty, significantly weakening network coherence and transmission link detection. By quantifying how extraction-induced errors propagate into epidemiological modeling outputs, the study demonstrates that optimized RNA extraction is critical not only for diagnostic accuracy but also for producing reliable and interpretable transmission networks. These findings underscore the need for standardized extraction practices and improved quality control frameworks to strengthen outbreak response systems and enhance public health decision-making.

Continuous manufacturing offers a sustainable and flexibleapproachfor fine chemical production, yet its application to complex agrochemicalslike tetraconazole remains largely unexplored. Herein, we report thefirst continuous-flow synthesis of the fungicide tetraconazole, addressingthe challenging catalytic synthesis of α-aryl acrylates. Wedemonstrate that a packed-bed flow reactor, equipped with a newlydesigned heterogeneous base catalyst, achieves unprecedented selectivityin the dehydrative aldol condensationa transformation thatpreviously suffered from poor conversion and yielded different majorproducts under batch conditions. This key reaction proceeds with highefficiency and selectivity for the first time in a continuous-flowsystem, resulting in the desired acrylate product (7).Kinetic analysis, supported by in situ monitoring using a high-temperaturesuperconductor (HTS) portable 200 MHz 1H NMR spectrometerwith an in-line cell, reveals that this flow-induced selectivity isnot merely due to enhanced mixing but stems from an accelerated interconversionequilibrium between crucial intermediates, effectively enabling adirect elimination pathway that bypasses the typically slow dehydrationstep. This robust catalytic strategy was successfully integrated intoa three-step sequential and continuous-flow process for the synthesisof the tetraconazole precursor, combining the catalytic dehydrativealdol condensation, the catalytic 1,4-addition of triazoles, and aflow ester reduction using LiBH4. Crucially, the integrationof the water-containing upstream process with the moisture-sensitivereduction was achieved via an efficient in-line liquid–liquidextraction module. This work provides an impactful example of applyingsophisticated reactor engineering and mechanistic insight into transforma historically nonselective batch reaction into a high-yielding (upto 74% overall) and fully integrated continuous manufacturing methodfor a complex pesticide.

ABSTRACT Globally, the ever‐rising energy demand has altered the techniques for producing oil, especially in the upstream processing, such as horizontal hydraulic fracturing and targeted drilling. Drilling deep oil and gas wells necessitates specialized drilling fluid formulations to ensure safe and efficient operations, as the conventional drilling fluids, such as the water‐based drilling fluids (WBDF), can cause shale swelling, and the oil‐based drilling fluids (OBDF) can cause other environmental concerns because of the presence of aromatic compounds. Synthetic‐based drilling fluids (SBDF) address these issues by combining superior performance with reduced environmental impact. Esters have shown the highest biodegradability and good performance as compared to other synthetic bases in drilling fluids. The present review article highlights the potential advantages of ester‐based drilling fluid (EBDF) under high‐pressure and high‐temperature (HPHT) environments. Moreover, the review articles show the advancement in the ester synthesis by using different carboxylic acids and oil feedstocks and provide beneficial insights on the recent advances in EBDF formulations. Furthermore, the review demonstrates EBDF cost efficiency over OBDF by comparison of formulation and disposal cost. This review also comprehends the studies that examined the utilization of various nanoparticles as a Pickering emulsion stabilizer in OBDF and SBDF formulations to enhance their properties and emulsion stabilities. Lastly, the review has proposed a futuristic formulation of drilling fluids via incorporating the nanoparticles that can improve the thermal stability of EBDF.

Recently, major e-commerce retailers like Amazon and Alibaba have started providing working capital loans to capital-constrained manufacturers selling through their marketplaces. Additionally, these platforms often introduce private labels (PLs), such as Amazon Basics, that compete with manufacturers' brands. This leads to a coopetative partnership between platforms and these small and medium enterprises, such as LonoLife, which compete with the platforms' PLs and also avail loans from them. Using game-theoretic analyses, we investigate the following question: How does the platform's PL introduction strategy impact a capital-constrained manufacturer's financing decision? The manufacturer manages the operational risk in its manufacturing process while selecting the optimal financing strategy, with or without the platform's PL. Intuitively, if the platform introduces the PL, as a strategic response, the manufacturer should consider opting for bank financing. However, the manufacturer does the opposite by switching to platform financing when the values of the production cost are within the intermediate range and the perceived quality of PL is low. Interestingly, the platform might adopt a cooperative strategy by not introducing the PL if the manufacturer decides to use platform financing. We recommend that the platform can utilise its PL effectively to mitigate operational risk in the upstream production process.

This study addresses the queuing inefficiencies caused by synchronized battery-swapping demands for electric trucks in open-pit mines. Through Discrete Event Simulation (DES), we identified systemic bottlenecks stemming from this synchronization. To mitigate this, we propose a hierarchical off-peak battery-swapping scheduling framework comprising an inner-layer Mixed-Integer Linear Programming (MILP) and an outer-layer Bayesian Optimization (BO) mechanism. Validated through three large-scale case studies, the model achieved 65% and 80% reductions in queuing times for single and dual loading platform scenarios, respectively, with 5.2%–5.7% improvements in transport throughput. Notably, expanding battery-swapping stations to four achieved equivalent efficiency gains (667 trips) as the optimization strategy (665 trips), highlighting the cost-effectiveness of intelligent scheduling over infrastructure scaling. Furthermore, in the third case study, by increasing loading platforms to alleviate constraints from upstream processes, the optimized model boosts transportation trips by up to 10%, demonstrating its capability to eliminate battery-swapping bottlenecks and fully unlock the potential of energy replenishment workflows.

Sedimentation, floodplain degradation, and altered hydrological regimes are major global challenges that undermine river basin resilience and water–food security. These pressures are most severe where upstream catchment processes and climate variability reshape downstream hydro-morphological systems. The north-eastern Haor floodplains of Bangladesh, particularly within the Om-Piyan-Dawki River system, exemplify these risks. Here, intense rainfall and runoff from Meghalaya accelerate sedimentation and flooding, with cascading impacts on agriculture, fisheries, and biodiversity. This study assesses sedimentation-induced risks to food security using a geospatial multi-index model that integrates Landsat imagery (1996–2021) with field observations. Results reveal a 904% increase in silted land and a 42% decline in water bodies, largely due to sand-dominated deposits. Wetlands, highly vulnerable to suspended sediment (>200 mg/L), expanded from 4% to 44%, severely affecting fisheries. The Sari-Gowain River’s water-carrying capacity declined threefold (2014–2018), while the Piyan River is nearing functional extinction, exacerbating biodiversity loss. Coupled with shifting rainfall patterns that aggravate flash floods, these changes reduced crop returns by 18%. The findings highlight the urgent need for integrated mitigation and adaptive management strategies to sustain ecological integrity, agricultural productivity, and water sustainability in flood-dependent systems worldwide.

Sustainable Aviation Fuel (SAF) is crucial for achieving carbon neutrality in the aviation sector. Among various production methods, Fischer–Tropsch (FT) synthesis using eco-friendly syngas has garnered significant attention. Two primary routes for producing syngas for FT synthesis—Dry Reforming of Methane (DRM) and Water Electrolysis combined with Reverse Water Gas Shift (WE&RWGS)—are actively being studied. As upstream processes, these routes are evaluated for their potential to provide low-carbon syngas for FT synthesis. However, comprehensive comparisons between these two pathways are limited, despite their importance for future technology planning and decision-making. In this study, we conduct a comparative evaluation of DRM- and WE&RWGS-based SAF production systems using virtual process design, along with life cycle assessment (LCA) and techno-economic analysis (TEA), to assess their environmental and economic viability as future technologies. LCA results indicate that the DRM-based route has more than four times lower environmental impact compared to the WE&RWGS-based system. The majority of the environmental burden arises from feedstock supply (CH4 and CO2) and energy inputs. TEA results suggest that while the base case scenario demonstrates limited economic feasibility, future scenarios that incorporate economies of scale and policy incentives show promise for long-term economic viability.

Microfluidics in biomanufacturing process development.

Developing a robust and scalable platform for AAV8 production.

The pulp and paper sector plays a crucial role in the national economy, acting as a significant source of foreign exchange earnings within the non-oil and gas sector. Despite this, challenges remain in exporting, particularly in managing the high volume of upstream industry products (pulp) and optimizing downstream operations. There is still potential for improvement to enhance the added value through the processing industry of pulp derivatives. This study aims to analyze the current state of the pulp and paper industry in Indonesia, map the value chain of the paper industry, explore strategic issues pertaining to the pulp sector, and develop strategies to boost the competitiveness of the Indonesian pulp industry. Conducted using qualitative methods, this research relies on both primary and secondary data from various sources and literature. Data analysis employed the PESTLE, VRIO, and SWOT approaches. The findings indicate that the pulp industry plays a vital role in Indonesia’s economy, as demonstrated by various economic, social, and other indicators. Presently, the industry is concentrated in Sumatra and predominantly driven by foreign direct investment (FDI). The pulp (and paper) supply chain operates on a pull-based model, with supply chain actors including raw material suppliers, manufacturers, distributors, and consumers. The issue of downstream strategy is addressed by designing alternative strategies across the pulp industry value chain to enhance value capture. These alternative strategies advocate for improvements from the upstream sector and processes to the downstream, including regulatory policies, supply assurance, process efficiency, product differentiation, and diversification in line with market demand.

Electro-assisted microalgae cultivation, harvesting, and recovery of high-value products: A review.