Abstract: Mechano-sorptive phenomena (MSP) refer to the coupled mechanical response of polymers under simultaneous mechanical stress and fluid sorption. The most researched MSP are environmental stress cracking (ESC) and mechano-sorptive creep (MSC). ESC initiates at regions of localized stress and solvent sorption, presenting as brittle fracture, while MSC is characterized by large, time-dependent, and partially recoverable creep associated with transient bulk sorption. ESC experiments can however also result in significant plastic deformation, in which case the term environmental stress yielding (ESY) has been used. Similarly, MSC can evolve into tertiary creep followed by rupture, in which case the phenomenon is termed mechano-sorptive creep rupture (MSCR). Both behaviors originate from solvent diffusion into the amorphous phase leading to disruption of non-covalent interactions between polymer chains. This review bridges seemingly disconnected research to illustrate that ESC and MSC represent extremes on a continuum of MSP, rather than disparate phenomena. We identify the principles of polymer thermodynamics and experimental methods necessary to separate polymer deformation under MSC into reversible stress-induced swelling and irreversible non-equilibrium deformation. We propose that a better understanding of these phenomena is necessary for a variety of applications including biomimetic materials that mimic the mechanical adaptability of marine organisms.

Abstract: Chimeric antigen receptor (CAR) T-cell therapy is an effective treatment for hematologic malignancies. However, it is limited by high costs, risk of severe toxicities such as cytokine release syndrome and neurotoxicity, and heterogeneous patient responses. Current therapy monitoring depends largely on subjective symptom assessment, routine laboratory tests, and basic vital signs, without real-time, quantitative evaluation of CAR T-cell expansion or activation in clinical practice. This lack of timely immune monitoring hampers individualized care and contributes to increased treatment costs. To address this need, we present a proof-of-concept, label-free Rapid Optical Imaging (ROI) biosensor with automated machine learning analysis for direct quantification of functional CAR T-cells from whole blood. This microfluidic platform integrates leukocyte separation, capture, and detection on a single chip, thereby eliminating centrifugation, staining, and operator-dependent interpretation. For validation, 50 μL whole blood samples spiked with Jurkat cells expressing a CD19 CAR underwent red blood cell depletion by agglutination and microfiltration. The leukocyte-enriched fraction was then incubated on a sensor chip functionalized with recombinant CD19 protein. Captured CAR T-cells were imaged by bright-field microscopy and automatically enumerated using a machine learning algorithm. A calibration curve was established across clinically relevant concentrations (1–1,000 cells/mL), with results validated against fluorescence microscopy and flow cytometry. This ROI biosensor enables rapid, quantitative, and label-free CAR T-cell detection from whole blood without specialized equipment or infrastructure. With further development, it could provide a cost-effective point-of-care tool for real-time immune monitoring and improved clinical management of patients receiving CAR T-cell therapy.

Abstract: Paradoxical insomnia is characterized by a discrepancy between subjective sleep com-plaints and objectively preserved sleep, yet its autonomic mechanisms remain poorly un-derstood. This study examined stage-specific autonomic characteristics of paradoxical insomnia using heart rate variability (HRV)–based statistical, multivariate, and machine learning analyses in a large population-based cohort. HRV features were extracted from non-overlapping five-minute windows across non–rapid eye movement (NREM) sleep, rapid eye movement (REM) sleep, and wake after sleep onset (WASO), and compared among paradoxical insomnia, objective insomnia, and normal sleep groups. Whole-night and consolidated sleep–stage HRV features showed substantial overlap among groups. In contrast, consistent stage-dependent differences emerged selectively during WASO, dur-ing which paradoxical insomnia exhibited distinct autonomic patterns relative to both comparison groups. Multivariate analysis showed the greatest group displacement dur-ing WASO, with UMAP centroid distances exceeding those observed during NREM and REM sleep. Supervised models trained on WASO-specific features achieved the highest classification performance, yielding an accuracy of 0.61 and an F1-score of 0.69 for para-doxical insomnia versus normal sleep, although overall discriminability remained mod-est. These findings indicate that autonomic alterations in paradoxical insomnia are pref-erentially expressed during post–sleep-onset wakefulness. Stage-resolved analysis identi-fies WASO as a physiologically informative window for objective phenotyping and for characterizing heterogeneity in insomnia subtypes.

Abstract: The increasing demand for recombinant proteins has driven innovation in bioprocessing strategies using Komagataella phaffii as a host organism. Conventional fed-batch cultivation with pure methanol induction remains widely used but presents challenges including high methanol consumption, extended downtime, and elevated operational costs. This study evaluates alternative strategies combining mixed induction (methanol/sorbitol) with continuous cultivation to enhance productivity, sustainability, and improved economic outcome. Using KEX2 protease as a model industrial recombinant protein, we compared four cultivation modes: fed-batch with methanol (benchmark), fed-batch with mixed induction, continuous with methanol, and continuous with mixed induction. Cell growth, volumetric yield, and specific productivity were evaluated at 5L scale and then modelled to simulate industrial scales (40 L and 400 L). Results demonstrate that continuous cultivation with mixed induction significantly improves yield up to 9-fold compared to conventional fed-batch and reduces methanol usage and oxygen demand. Techno-economic simulations reveal that a 40 L continuous process can match or exceed the output of two 400 L fed-batch runs, while lowering capital and operating costs and minimising environmental footprint. This integrated strategy offers a scalable, cost-effective, and safer alternative for recombinant protein production, supporting the development of compact and sustainable manufacturing platform.