Marangoni Droplets of Dextran in PEG Solution and Its Motile Change Due to Coil-Globule Transition of Coexisting DNA.

Motile droplets using Marangoni convection are attracting attention for their potential as cell-mimicking small robots. However, the motion of droplets relative to the internal and external environments that generate Marangoni convection has not been quantitatively described. In this study, we used an aqueous two-phase system [poly(ethylene glycol) (PEG) and dextran] in an elongated chamber to generate motile dextran droplets in a constant PEG concentration gradient. We demonstrated that dextran droplets move by Marangoni convection, resulting from the PEG concentration gradient and the active transport of PEG and dextran into and out of the motile dextran droplet. Furthermore, by spontaneously incorporating long DNA into the dextran droplets, we achieved cell-like motility changes controlled by coexisting environment-sensing molecules. The DNA changes its position within the droplet and motile speed in response to external conditions. In the presence of Mg2+, the coil-globule transition of DNA inside the droplet accelerates the motile speed due to the decrease in the droplet's dynamic viscosity. Globule DNA condenses at the rear part of the droplet along the convection, while coil DNA moves away from the droplet's central axis, separating the dipole convections. These results provide a blueprint for designing autonomous small robots using phase-separated droplets, which change the mobility and molecular distribution within the droplet in reaction with the environment. It will also open unexplored areas of self-assembly mechanisms through phase separation under convections, such as intracellular phase separation.

Advanced electrochemical membrane technologies for near-complete resource recovery and zero-discharge of urine: Performance optimization and evaluation.

The depletion of nutrient sources in fertilizers demands a paradigm shift in the treatment of nutrient-rich wastewater, such as urine, to enable efficient resource recovery and high-value conversion. This study presented an integrated bipolar membrane electrodialysis (BMED) and hollow fiber membrane (HFM) system for near-complete resource recovery and zero-discharge from urine treatment. Computational simulations and experimental validations demonstrated that a higher voltage (20 V) significantly enhanced energy utilization, while an optimal flow rate of 0.4 L/min effectively mitigated the negative effects of concentration polarization and electro-osmosis on system performance. Within 40 min, the process separated 90.13% of the salts in urine, with an energy consumption of only 8.45 kWh/kgbase. Utilizing a multi-chamber structure for selective separation, the system achieved recovery efficiencies of 89% for nitrogen, 96% for phosphorus, and 95% for potassium from fresh urine, converting them into high-value products such as 85 mM acid, 69.5 mM base, and liquid fertilizer. According to techno-economic analysis, the cost of treating urine using this system at the lab-scale was $6.29/kg of products (including acid, base, and (NH4)2SO4), which was significantly lower than the $20.44/kg cost for the precipitation method to produce struvite. Excluding fixed costs, a net profit of $18.24/m3 was achieved through the recovery of valuable products from urine using this system. The pilot-scale assessment showed that the net benefit amounts to $19.90/m3 of urine, demonstrating significant economic feasibility. This study presents an effective approach for the near-complete resource recovery and zero-discharge treatment of urine, offering a practical solution for sustainable nutrient recycling and wastewater management.

Gas chromatographic techniques and spectroscopic approaches for a deep characterization of Piper gaudichaudianum Kunth essential oil from Brazil.

Piper gaudichaudianum Kunth essential oil (EO) is a natural source of bioactive components, having multiple therapeutic applications. Its chemical composition is highly variable, and strictly depends on abiotic factors, resulting in various biological activities. The present study details the utilization of multiple gas chromatographic techniques alongside nuclear magnetic resonance (NMR) spectroscopy to characterize the essential oil of Piper gaudichaudianum Kunth from Brazil. Seventy-six components were identified using GC-MS analysis, while enantio­selective multidimensional gas chromatography elucidated the enantiomeric distribution of eight chiral components, for the first time in the literature. Following GC-MS analysis, an unidentified component, constituting approximately 27 % of the total oil, prompted an isolation step through preparative gas chromatography. Through the combined use of nuclear magnetic resonance, GC-Fourier transform infrared spectroscopy (FTIR), and mass spectrometry (MS), the unknown molecule was structurally identified as 4-[(3E)­dec-3-en-1-yl]phenol. Remarkably, it was identified as a known molecule, gibbilimbol B, and not previously listed in any MS database. Subsequently, the spectrum was included in a commercial library, specifically the FFNSC 4.0 MS database, for the first time.

Membrane chromatography for AAV full capsid enrichment: Process development to scale up.

The recent FDA approval of several adeno-associated virus (AAV)-based gene therapies is driving demand for AAV production. One of the biggest AAV manufacturing challenges is removing "empty" capsids, which do not contain the gene of interest. Anion exchange chromatography has emerged as the leading solution for scalable full capsid enrichment. Here we develop a process for the baseline separation of empty and full AAV capsids using anion exchange membrane chromatography. This process development approach utilized AAV serotypes 8 and 9 and traverses initial screening of separation conditions up to manufacturing-scale processes. Process development of a two-step elution was performed via response surface DoE, exploring conductivity and the length of the first elution step. The results from response surfaces were used to construct statistical models of the process operating space. These models provide optimal conditions for recovery and purity, both of which can exceed 70 %. Model predictions were then validated at small scale prior to scale-up. We present the results from our scale-up purification and show that purity and yield are consistent with the results obtained from the response surface model.

Tuning the functionality of designer translating organelles with orthogonal tRNA synthetase/tRNA pairs.

Site-specific incorporation of noncanonical amino acids (ncAAs) can be realized by genetic code expansion (GCE) technology. Different orthogonal tRNA/synthetases (RS/tRNA) pairs have been developed to introduce a ncAA at the desired site, delivering a wide variety of functionalities that can be installed into selected proteins. Cytoplasmic expression of RS/tRNA pairs can cause a problem with background ncAA incorporation into host proteins. The application of orthogonally translating organelles (OTOs), inspired by the concept of phase separation, provides a solution for this issue in mammalian cells, allowing site-specific and protein-selective ncAA incorporation. So far, only Methanosarcina mazei (Mm) PylRS has been used with OTOs, limiting the method's potential. Here, we explored the implementation of four other widely used orthogonal RS/tRNA pairs with OTOs, which, to our surprise, were unsuccessful in generating mRNA-selective GCE. Next, we tested several experimental solutions to develop a new chimeric phenylalanyl-RS/tRNA pair that enables ncAA incorporation in OTOs, site-specific and protein-selective. Our work reveals unaccounted design constraints in the spatial engineering of enzyme functions using designer organelles and presents a strategy to overcome those in vivo. We then discuss current limitations and future directions of in-cell engineering in general and protein engineering using GCE specifically.

The Formation Mechanism of Carbonized Polymer Dots: Crosslinking-Induced Nucleation and Carbonization.

Carbon dots (CDs), as a kind of zero-dimensional nanomaterials, have been widely synthesized by bottom-up methods from various precursors. However, the formation mechanism is still unclear and controversial, which also brings difficulty to the regulation of structures and properties. Only some tentative formation processes were postulated by analyzing the products obtained at different reaction times and temperatures. Here, the effect of crosslinking on the formation of carbonized polymer dots (CPDs) is explored. Crosslinking-induced nucleation and carbonization (CINC) is proposed as the driving force for the formation of CPDs. Under hydrothermal synthesis, the precursors are initiated to polymerize and crosslink. The crosslinking brings higher hydrophobicity to generate the hydrophilic/hydrophobic microphase separation, which promotes dehydration and carbonization resulting in the formation of CPDs. Based on the principle of CINC, the influence factors of size are also revealed. Moreover, the dissipative particle dynamics (DPD) simulation is employed to support this formation mechanism. This concept of CINC will bring light to the formation process of CPDs, as well as facilitate the regulation of CPDs' size and photoluminescence.

Selective Segregation of Thermo-Responsive Microgels via Microfluidic Technology.

Separation of equally sized particles distinguished solely by material properties remains still a very challenging task. Here a simple separation of differently charged, thermo-responsive polymeric particles (for example microgels) but equal in size, via the combination of pressure-driven microfluidic flow and precise temperature control is proposed. The separation principle relies on forcing thermo-responsive microgels to undergo the volume phase transition during heating and therefore changing its size and correspondingly the change in drift along a pressure driven shear flow. Different thermo-responsive particle types such as different grades of ionizable groups inside the polymer matrix have different temperature regions of volume phase transition temperature (VPTT). This enables selective control of collapsed versus swollen microgels, and accordingly, this physical principle provides a simple method for fractioning a binary mixture with at least one thermo-responsive particle, which is achieved by elution times in the sense of particle chromatography. The concepts are visualized in experimental studies, with an intend to improve the purification strategy of the broad distribution of charged microgels into fractioning to more narrow distribution microgels distinguished solely by slight differences in net charge.

Fabrication of rGO-bridged TiO2/g-C3N4 Z-scheme Nanocomposites via Pulsed Laser Ablation for Efficient Photocatalytic CO2 Reduction.

Highly efficient photocatalysts can be fabricated using favorable charge transfer nanocomposite channel structures. This study adopted pulsed laser ablation in liquid (PLAL) to obtain rGO-bridged TiO2/g-C3N4 (rGO-TiO2/g-C3N4) photocatalytic Z-scheme without the need for noble metals. In addition to evaluating the resulting nanocomposite's (comprising rGO nanosheets, TiO2 nanotubes, and g-C3N4 nanosheets) CO2 reduction effectiveness, its chemical, morphological, structural, and optical characteristics were examined using various analytical techniques. The findings revealed a synergistic interaction between g-C3N4 and TiO2, suggesting the presence of unique interfacial bonding, as well as enhanced visible light absorption. Notably, the ternary rGO-TiO2/g-C3N4 Z-scheme exhibits an excellent photocatalytic performance by photocatalytically converting CO2 into CO and CH4, with 81% selectivity towards the CO and 1.91% apparent quantum efficiency at 420 nm. Thus, the findings can pave the way for various Z-scheme systems in wide photocatalytic applications.

Recent advances in high-resolution traveling wave-based ion mobility separations coupled to mass spectrometry.

Recently, ion mobility spectrometry-mass spectrometry (IMS-MS) has become more readily incorporated into various omics-based workflows. These growing applications are due to developments in instrumentation within the last decade that have enabled higher-resolution ion mobility separations. Two such platforms are the cyclic (cIMS) and structures for lossless ion manipulations (SLIM), both of which use traveling wave ion mobility spectrometry (TWIMS). High-resolution separations achieved with these techniques stem from the drastically increased pathlengths, on the order of 10 s of meters to >1 km, in both cIMS-MS and SLIM IMS-MS, respectively. Herein, we highlight recent developments and advances, for the period 2019-2023, in high-resolution traveling wave-based IMS-MS through instrumentation, calibration strategies, hyphenated techniques, and applications. Specifically, we will discuss applications including CCS calculations in multipass IMS-MS separations, coupling of IMS-MS with chromatography, imaging, and cryogenic infrared spectroscopy, and isomeric separations of glycans, lipids, and other small metabolites.

Effects of the Regular Use of Virtual Environments on Spatial Navigation and Memory.

Introduction: The cognitive effects of video games have garnered increasing attention due to their potential applications in cognitive rehabilitation and evaluation. However, the underlying mechanisms driving these cognitive modifications remain poorly understood. Objectives: This study investigates the fundamental mnemonic processes of spatial navigation, pattern separation, and recognition memory, closely associated with the hippocampus. Our objective is to elucidate the interaction of these cognitive processes and shed light on rehabilitation mechanisms that could inform the design of video games aimed at stimulating the hippocampus. Method: In this study, we assessed 48 young adults, including both video game players and non-players. We utilized virtual reality and cognitive tasks such as the Lobato Virtual Water Maze and the Mnemonic Similarity Task to evaluate their cognitive abilities. Results: Our key findings highlight that gamers exhibit heightened pattern separation abilities and demonstrate quicker and more accurate spatial learning, attributed to the cognitive stimulation induced by video games. Additionally, we uncovered a significant relationship between spatial memory, guided by environmental cues, and pattern separation, which serves as the foundation for more efficient spatial navigation. Conclusions: These results provide valuable insights into the cognitive impact of video games and offer potential for monitoring changes in rehabilitation processes and early signs of cognitive decline through virtual reality-based assessments. Ultimately, we propose that examining the relationships between cognitive processes represents an effective method for evaluating neurodegenerative conditions, offering new possibilities for early diagnosis and intervention.

Discrimination of semantically similar verbal memory traces is affected in healthy aging.

Mnemonic discrimination of highly similar memory traces is affected in healthy aging via changes in hippocampal pattern separation-i.e., the ability of the hippocampus to orthogonalize highly similar neural inputs. The decline of this process leads to a loss of episodic specificity. Because previous studies have almost exclusively tested mnemonic discrimination of visuospatial stimuli (e.g., objects or scenes), less is known about age-related effects on the episodic specificity of semantically similar traces. To address this gap, we designed a task to assess mnemonic discrimination of verbal stimuli as a function of semantic similarity based on word embeddings. Forty young (Mage = 21.7 years) and 40 old adults (Mage = 69.8 years) first incidentally encoded adjective-noun phrases, then performed a surprise recognition test involving exactly repeated and highly similar lure phrases. We found that increasing semantic similarity negatively affected mnemonic discrimination in both age groups, and that compared to young adults, older adults showed worse discrimination at medium levels of semantic similarity. These results indicate that episodic specificity of semantically similar memory traces is affected in aging via less efficient mnemonic operations and strengthen the notion that mnemonic discrimination is a modality-independent process supporting memory specificity across representational domains.

Colorimetric aptasensor for Listeria monocytogenes detection using dual functional Fe3O4@MIL-100(Fe) with magnetic separation and oxidase-like activities in food samples.

A novel colorimetric aptasensor assay based on the excellent magnetic responsiveness and oxidase-like activity of Fe3O4@MIL-100(Fe) was developed. Fe3O4@MIL-100(Fe) absorbed with aptamer and blocked by BSA served as capture probe for selective isolation and enrichment of Listeria monocytogenes one of the most common and dangerous foodborne pathogenic bacteria. The aptamer absorbed on Fe3O4@MIL-100(Fe) was further used as signal probe that specifically binds with target bacteria conjugation of capture probe for colorimetric detection of Listeria monocytogenes, taking advantages of its oxidase-like activity. The linear range of the detection of Listeria monocytogenes was from 102 to 107 CFU mL-1, with the limit of detection as low as 14 CFU mL-1. The approach also showed good feasibility for detection of Listeria monocytogenes in milk and meat samples. The spiked recoveries were in the range 81-114% with relative standard deviations ranging from 1.28 to 5.19%. Thus, this work provides an efficient, convenient, and practical tool for selective isolation and colorimetric detection of Listeria monocytogenes in food.

PSAR-SR: Patches separation and artifacts removal for improving super-resolution networks.

The success of the ClassSR has led to a strategy of decomposing images being used for large image SR. The decomposed image patches have different recovery difficulties. Therefore, in ClassSR, image patches are reconstructed by different networks to greatly reduce the computational cost. However, in ClassSR, the training of multiple sub-networks inevitably increases the training difficulty. Furthermore, decomposing images with overlapping not only increases the computational cost but also inevitably produces artifacts. To address these challenges, we propose an end-to-end general framework, named patches separation and artifacts removal SR (PSAR-SR). In PSAR-SR, we propose an image information complexity module (IICM) to efficiently determine the difficulty of recovering image patches. Then, we propose a patches classification and separation module (PCSM), which can dynamically select an appropriate SR path for image patches of different recovery difficulties. Moreover, we propose a multi-attention artifacts removal module (MARM) in the network backend, which can not only greatly reduce the computational cost but also solve the artifacts problem well under the overlapping-free decomposition. Further, we propose two loss functions - threshold penalty loss (TP-Loss) and artifacts removal loss (AR-Loss). TP-Loss can better select appropriate SR paths for image patches. AR-Loss can effectively guarantee the reconstruction quality between image patches. Experiments show that compared to the leading methods, PSAR-SR well eliminates artifacts under the overlapping-free decomposition and achieves superior performance on existing methods (e.g., FSRCNN, CARN, SRResNet, RCAN and CAMixerSR). Moreover, PSAR-SR saves 53%-65% FLOPs in computational cost far beyond the leading methods. The code will be made available: https://github.com/dywang95/PSAR-SR.

PRMT1 and TDRD3 promote stress granule assembly by rebuilding the protein-RNA interaction network.

Stress granules (SGs) are membrane-less organelles (MLOs) or cytosolic compartments formed upon exposure to environmental cell stress-inducing stimuli. SGs are based on ribonucleoprotein complexes from a set of cytoplasmic proteins and mRNAs, blocked in translation due to stress cell-induced polysome disassembly. Post-translational modifications (PTMs) such as methylation, are involved in SG assembly, with the methylation writer PRMT1 and its reader TDRD3 colocalizing to SGs. However, the role of this writer-reader system in SG assembly remains unclear. Here, we found that PRMT1 methylates SG constituent RNA-binding proteins (RBPs) on their RGG motifs. Besides, we report that TDRD3, as a reader of asymmetric dimethylarginines, enhances RNA binding to recruit additional RNAs and RBPs, lowering the percolation threshold and promoting SG assembly. Our study enriches our understanding of the molecular mechanism of SG formation by elucidating the functions of PRMT1 and TDRD3. We anticipate that our study will provide a new perspective for comprehensively understanding the functions of PTMs in liquid-liquid phase separation driven condensate assembly.

Optimization of pre-enrichment strategies for mouse hematopoietic stem cell isolation and metabolomic analysis.

Blood cell production arises from the activity of hematopoietic stem cells (HSCs), defined by their self-renewal capacity and ability to give rise to all mature blood cell types. The mouse remains one of the most studied species in hematological research, and markers to define and isolate mouse HSCs are well-established. Given the very low frequency of HSCs in the bone marrow, stem cell pre-enrichment by red blood cell lysis and magnetic cell separation is often performed as part of the isolation process to reduce sorting times. Several pre-enrichment strategies are available, differing in their speed, degree of enrichment, final cell yield and cost. In the current study, we performed a side-by-side comparison and provide a decision tree to help researchers select a pre-enrichment strategy for mouse HSC isolation depending on their downstream application. We then compared different pre-enrichment techniques in combination with metabolomics analysis of HSCs, where speed, yield and temperature during pre-enrichment are crucial factors, and found that the choice of pre-enrichment strategy significantly impacts the number of metabolites detected and levels of individual metabolites in HSCs.

Separation of Pd from Pt and Rh by solvent extraction method from waste solution.

The paper investigated the possibility of extractive separation of palladium from platinum and rhodium with ionic liquid Cyphos IL 101. A technological solution obtained by dissolving waste materials was used as the test material. Based on the experiments performed, it was found that a 10% (v/v) solution of the Cyphos IL 101 ionic liquid in toluene allows the extraction of both Pd and Pt with an efficiency of 99% from the initial solution when extraction is carried out at the pH 0.5, vorg:vaq phase ratio 1:1 and contact time of 15 min. Moreover, the research proved that it is possible to separate Pd from Pt at the stripping stage using a 0.1 mol/dm3 thiourea solution while maintaining a high selectivity coefficient.

Biophysical characterization of the phase separation of TDP-43 devoid of the C-terminal domain.

BACKGROUND: Frontotemporal lobar degeneration with ubiquitin-positive inclusions (FTLD-TDP), amyotrophic lateral sclerosis (ALS) and limbic-predominant age-related TDP-43 encephalopathy (LATE) are associated with deposition of cytoplasmic inclusions of TAR DNA-binding protein 43 (TDP-43) in neurons. One complexity of this process lies in the ability of TDP-43 to form liquid-phase membraneless organelles in cells. Previous work has shown that the recombinant, purified, prion-like domain (PrLD) forms liquid droplets in vitro, but the behaviour of the complementary fragment is uncertain. METHODS: We have purified such a construct without the PrLD (PrLD-less TDP-43) and have induced its phase separation using a solution-jump method and an array of biophysical techniques to study the morphology, state of matter and structure of the TDP-43 assemblies. RESULTS: The fluorescent TMR-labelled protein construct, imaged using confocal fluorescence, formed rapidly (< 1 min) round, homogeneous and 0.5-1.0 µm wide assemblies which then coalesced into larger, yet round, species. When labelled with AlexaFluor488, they initially exhibited fluorescence recovery after photobleaching (FRAP), showing a liquid behaviour distinct from full-length TDP-43 and similar to PrLD. The protein molecules did not undergo major structural changes, as determined with circular dichroism and intrinsic fluorescence spectroscopies. This process had a pH and salt dependence distinct from those of full-length TDP-43 and its PrLD, which can be rationalized on the grounds of electrostatic forces. CONCLUSIONS: Similarly to PrLD, PrLD-less TDP-43 forms liquid droplets in vitro through liquid-liquid phase separation (LLPS), unlike the full-length protein that rather undergoes liquid-solid phase separation (LSPS). These results offer a rationale of the complex electrostatic forces governing phase separation of full-length TDP-43 and its fragments. On the one hand, PrLD-less TDP-43 has a low pI and oppositively charged domains, and LLPS is inhibited by salts, which attenuate inter-domain electrostatic attractions. On the other hand, PrLD is positively charged due to a high isoionic point (pI) and LLPS is therefore promoted by salts and pH increases as they both reduce electrostatic repulsions. By contrast, full-length TDP-43 undergoes LSPS most favourably at its pI, with positive and negative salt dependences at lower and higher pH, respectively, depending on whether repulsive or attractive forces dominate, respectively.

Healable, Recyclable, and Upcyclable Gel Membranes for Efficient Carbon Dioxide Separation.

Ionic liquids (ILs) are prized for their selective dissolution of carbon dioxide (CO2), leading to their widespread use in ionogel membranes for gas separation. Despite their advantages, creating sustainable ionogel membranes with high IL contents poses challenges due to limited mechanical strength, leakage risks, and poor recyclability. Herein, we leverage copolymerized and supramolecularly bound ILs to develop ionogel membranes with high mechanical strength, zero leakage, and excellent self-healing and recycling capabilities. These membranes exhibit superior ideal selectivity for gas separation compared to other reported ionogel membranes, achieving a CO2/nitrogen selectivity of 61.7 and a CO2/methane selectivity of 24.6, coupled with an acceptable CO2 permeability of 186.4 Barrer. Additionally, these gas separation ionogel membranes can be upcycled into ionic skins for sensing applications, further enhancing their utility. This research outlines a strategic approach to molecularly engineer ionogel membranes, offering a promising pathway for developing sustainable, high-performance materials for advanced gas separation technologies.

Adaptation processes in Halomicronema hongdechloris, an example of the light-induced optimization of the photosynthetic apparatus on hierarchical time scales.

Oxygenic photosynthesis in Halomicronema hongdechloris, one of a series of cyanobacteria producing red-shifted Chl f, is adapted to varying light conditions by a range of diverse processes acting over largely different time scales. Acclimation to far-red light (FRL) above 700 nm over several days is mirrored by reversible changes in the Chl f content. In several cyanobacteria that undergo FRL photoacclimation, Chl d and Chl f are directly involved in excitation energy transfer in the antenna system, form the primary donor in photosystem I (PSI), and are also involved in electron transfer within photosystem II (PSII), most probably at the ChlD1 position, with efficient charge transfer happening with comparable kinetics to reaction centers containing Chl a. In H. hongdechloris, the formation of Chl f under FRL comes along with slow adaptive proteomic shifts like the rebuilding of the D1 complex on the time scale of days. On shorter time scales, much faster adaptation mechanisms exist involving the phycobilisomes (PBSs), which mainly contain allophycocyanin upon adaptation to FRL. Short illumination with white, blue, or red light leads to reactive oxygen species-driven mobilization of the PBSs on the time scale of seconds, in effect recoupling the PBSs with Chl f-containing PSII to re-establish efficient excitation energy transfer within minutes. In summary, H. hongdechloris reorganizes PSII to act as a molecular heat pump lifting excited states from Chl f to Chl a on the picosecond time scale in combination with a light-driven PBS reorganization acting on the time scale of seconds to minutes depending on the actual light conditions. Thus, structure-function relationships in photosynthetic energy and electron transport in H. hongdechloris including long-term adaptation processes cover 10-12 to 106 seconds, i.e., 18 orders of magnitude in time.

New policies on skin-to-skin contact warrant an oxytocin-based perspective on perinatal health care.

Background: In 2023, the World Health Organization (WHO) published a Global Position Paper on Kangaroo Mother Care (KMC), which is applicable to all countries worldwide: from the moment of birth, every "small and sick" newborn should remain with mother in immediate and continuous skin-to-skin contact (SSC), receiving all required clinical care in that place. This was prompted by the startling results of a randomized controlled trial published in 2021: in which 1,609 infants receiving immediate SSC were compared with 1,602 controls that were separated from their mothers but otherwise received identical conventional state-of-the-art care. The intervention infants showed a 25% reduction in mortality after 28 days. New perspectives: The new WHO guidelines are a significant change from earlier guidance and common clinical practice. The author presents that separating mothers and babies is assumed to be "normal" (a paradigm) but actually puts newborns at increased risk for morbidity and mortality. The author presents arguments and ethical perspectives for a new perspective on what is "normal," keeping newborns with their mothers is the infant's physiological expectation and critical requirement for healthy development. The author reviews the scientific rationale for changing the paradigm, based on synchronous interactions of oxytocin on both mother and infant. This follows a critique of the new policies that highlights the role of immediate SSC. Actionable recommendations: This critique strengthens the case for implementing the WHO guidelines on KMC for small and sick babies. System changes will be necessary in both obstetric and neonatal settings to ensure seamless perinatal care. Based on the role of oxytocin, the author identifies that many current routine care practices may actually contribute to stress and increased vulnerability to the newborn. WHO has actionable recommendations about family involvement and presence in newborn intensive care units. Discussion: The concepts of resilience and vulnerability have specific definitions well known in perinatal care: the key outcome of care should be resilience rather than merely the absence of vulnerability. Newborns in all settings and contexts need us to re-evaluate our paradigms and adopt and implement the new WHO guidelines on KMC in perinatal care.