Immunoengineering can overcome the glycocalyx armour of cancer cells.

Cancer cell glycocalyx is a major line of defence against immune surveillance. However, how specific physical properties of the glycocalyx are regulated on a molecular level, contribute to immune evasion and may be overcome through immunoengineering must be resolved. Here we report how cancer-associated mucins and their glycosylation contribute to the nanoscale material thickness of the glycocalyx and consequently modulate the functional interactions with cytotoxic immune cells. Natural-killer-cell-mediated cytotoxicity is inversely correlated with the glycocalyx thickness of the target cells. Changes in glycocalyx thickness of approximately 10 nm can alter the susceptibility to immune cell attack. Enhanced stimulation of natural killer and T cells through equipment with chimeric antigen receptors can improve the cytotoxicity against mucin-bearing target cells. Alternatively, cytotoxicity can be enhanced through engineering effector cells to display glycocalyx-editing enzymes, including mucinases and sialidases. Together, our results motivate the development of immunoengineering strategies that overcome the glycocalyx armour of cancer cells.

Lysine-372-dependent SUMOylation inhibits the enzymatic activity of glutamine synthases.

Glutamine synthetase (GS) is a crucial enzyme involved in de novo synthesis of glutamine and participates in several biological processes, including nitrogen metabolism, nucleotide synthesis, and amino acid synthesis. Post-translational modification makes GS more adaptable to the needs of cells, and acetylation modification of GS at double sites has attracted considerable attention. Despite very intensive research, how SUMOylation affects GS activity at a molecular level remains unclear. Here, we report that previously undiscovered GS SUMOylation which is deficient mutant K372R of GS exhibits more bluntness under glutamine starvation. Mechanistically, glutamine deprivation triggers the GS SUMOylation, and this SUMOylation impaired the protein stability of GS, within a concomitant decrease in enzymatic activity. In addition, we identified SAE1, Ubc9, and PIAS1 as the assembly enzymes of GS SUMOylation respectively. Furthermore, Senp1/2 functions as a SUMO-specific protease to reverse the SUMOylation of GS. This study provides the first evidence that SUMOylation serves as a regulatory mechanism for determining the GS enzymatic activity, contributing to understanding the GS regulation roles in various cellular and pathophysiological processes.

Azo-Cyanamide Bridged Dinuclear Iron Complexes Exhibiting no Electronic Coupling but Moderate Magnetic Coupling between the two Iron Centers.

To investigate the effect of long-distance organic ligand on electronic coupling between metallic atoms, the mononuclear and dinuclear complexes [Cp(dppe)Fe(apc)] (1), [{Cp(dppe)Fe}2(µ-adpc)] (2), [{CpMe5(dppe)Fe}2(µ-adpc) (3) and their oxidized complexes [Cp(dppe)Fe(apc)][PF6] (1[PF6]), [{Cp(dppe)Fe}2(µ-adpc)][PF6] (2[PF6]2), [{CpMe5(dppe)Fe}2(µ-adpc)][PF6]2 (3[PF6]2) (Cp=1,3-cyclopentadiene, CpMe5=1,2,3,4,5-pentamethylcyclopentadiene, dppe=1,2-bis(diphenylphosphino)ethane), apc-=4-azo(phenylcyanamido)benzene and adpc2-=4,4'-azodi(phenylcyanamido)) were synthesized and characterized by cyclic voltammetry, UV-vis, single-crystal X-ray diffraction and Mössbauer spectra. Electrochemical measurements showed no electronic coupling between the two terminal Fe units, However, the investigation results of the magnetic properties of the two-electron oxidized complexes indicate the presence of moderate antiferromagnetic coupling across 18 Šdistance.

De Garengeot Hernia, an acute appendicitis in the right femoral hernia canal, and successful management with transabdominal closure and appendectomy: a case Report.

Incarceration of the appendix within a femoral hernia is a rare condition of abdominal wall hernia about 0.1 to 0.5% in reported femoral hernia [1]. We report a case of a 56-year-old female whose appendix was trapped in the right femoral canal. There are few reports in the literature on entrapment of the appendix within a femoral hernia. The management of this condition includes antibiotics, drainage appendectomy, hernioplasty and mesh repair.

Coupled folding-upon-binding of human tumor suppressor MIG6 to lung cancer EGFR kinase domain and molecular trimming/stapling of MIG6-derived ß-hairpins to target the coupling event.

Human epidermal growth factor receptor (EGFR) is involved in strong association with malignant proliferation, which has been shown to play a central role in the development and progression of non-small cell lung cancer and other solid tumors. The tumor-suppressor protein MIG6 is a negative regulator of EGFR kinase activity by binding at the activation interface of asymmetric dimer of EGFR kinase domain to disrupt EGFR dimerization and then inactivate the kinase. The protein adopts two discrete fragments 1 and 2 to directly interact with EGFR. It is revealed that the MIG6 fragment 2 is intrinsically disordered in free unbound state, but would fold into a well-structured ß-hairpin when binding to EGFR, thus characterized by a so-called coupled folding-upon-binding process, which can be regarded as a compromise between favorable direct readout and unfavorable indirect readout. Here, a 23-mer F2P peptide was derived from MIG6 fragment 2, trimmed into a 17-mer tF2P peptide that contains the binding hotspot region of the fragment 2, and then constrained with an ordered hairpin conformation in free unbound state by disulfide stapling, finally resulting in a rationally stapled/trimmed stF2P peptide that largely minimizes the unfavorable indirect readout effect upon its binding to EGFR kinase domain, with affinity improved considerably upon the trimming and stapling/trimming. These rationally designed ß-hairpin peptides may be further exploited as potent anti-lung cancer agents to target the activation event of EGFR dimerization.

PLIN2 promotes HCC cells proliferation by inhibiting the degradation of HIF1α.

PLIN2 has been found to be dysregulated in several human malignancies, which influences cancer progression. However, the roles of PLIN2 in regulating hepatocellular carcinoma (HCC) progression are still unclear. Here, we revealed that PLIN2 was frequently upregulated in HCC cells and tissues, and increased PLIN2 expression was associated with poor prognosis outcomes in HCC. In HCC cells, overexpressing PLIN2 promoted cell proliferation, PLIN2-deficiency inhibited cell vitality. Mechanistically, silencing of PLIN2 expression downregulated hypoxia inducible factor 1-α (HIF1α) expression and this downregulation in turn inhibited the targeting genes of HIF1α. Furthermore, we found that PLIN2 stabilized and retarded the degradation of the HIF1α through autophagy-lysosomal pathway by inhibiting AMPK/ULK1. Collectively, we clarified the carcinogenic role of PLIN2 in HCC and suggested a prognostic biomarker for diagnosis and clinical therapy in the future.

ZNF205 positively regulates RLR antiviral signaling by targeting RIG-I.

Retinoic acid-inducible gene I (RIG-I) is a cytosolic viral RNA receptor. Upon viral infection, the protein recognizes and then recruits adapter protein mitochondrial antiviral signaling (MAVS) protein, initiating the production of interferons and proinflammatory cytokines to establish an antiviral state. In the present study, we identify zinc finger protein 205 (ZNF205) which associates with RIG-I and promotes the Sendai virus (SeV)-induced antiviral innate immune response. Overexpression of ZNF205 facilitates interferon-beta (IFN-ß) introduction, whereas ZNF205 deficiency restricts its introduction. Mechanistically, the C-terminal zinc finger domain of ZNF205 interacts with the N-terminal tandem caspase recruitment domains (CARDs) of RIG-I; this interaction markedly promotes K63 ubiquitin-linked polyubiquitination of RIG-I, which is crucial for RIG-I activation. Thus, our results demonstrate that ZNF205 is a positive regulator of the RIG-I-mediated innate antiviral immune signaling pathway.

Semiparametric predictive inference for failure data using first-hitting-time threshold regression.

The progression of disease for an individual can be described mathematically as a stochastic process. The individual experiences a failure event when the disease path first reaches or crosses a critical disease level. This happening defines a failure event and a first hitting time or time-to-event, both of which are important in medical contexts. When the context involves explanatory variables then there is usually an interest in incorporating regression structures into the analysis and the methodology known as threshold regression comes into play. To date, most applications of threshold regression have been based on parametric families of stochastic processes. This paper presents a semiparametric form of threshold regression that requires the stochastic process to have only one key property, namely, stationary independent increments. As this property is frequently encountered in real applications, this model has potential for use in many fields. The mathematical underpinnings of this semiparametric approach for estimation and prediction are described. The basic data element required by the model is a pair of readings representing the observed change in time and the observed change in disease level, arising from either a failure event or survival of the individual to the end of the data record. An extension is presented for applications where the underlying disease process is unobservable but component covariate processes are available to construct a surrogate disease process. Threshold regression, used in combination with a data technique called Markov decomposition, allows the methods to handle longitudinal time-to-event data by uncoupling a longitudinal record into a sequence of single records. Computational aspects of the methods are straightforward. An array of simulation experiments that verify computational feasibility and statistical inference are reported in an online supplement. Case applications based on longitudinal observational data from The Osteoarthritis Initiative (OAI) study are presented to demonstrate the methodology and its practical use.

Estimation and testing for clustered interval-censored bivariate survival data with application using the semi-parametric version of the Clayton-Oakes model.

The Kaplan-Meier estimator is ubiquitously used to estimate survival probabilities for time-to-event data. It is nonparametric, and thus does not require specification of a survival distribution, but it does assume that the risk set at any time t consists of independent observations. This assumption does not hold for data from paired organ systems such as occur in ophthalmology (eyes) or otolaryngology (ears), or for other types of clustered data. In this article, we estimate marginal survival probabilities in the setting of clustered data, and provide confidence limits for these estimates with intra-cluster correlation accounted for by an interval-censored version of the Clayton-Oakes model. We develop a goodness-of-fit test for general bivariate interval-censored data and apply it to the proposed interval-censored version of the Clayton-Oakes model. We also propose a likelihood ratio test for the comparison of survival distributions between two groups in the setting of clustered data under the assumption of a constant between-group hazard ratio. This methodology can be used both for balanced and unbalanced cluster sizes, and also when the cluster size is informative. We compare our test to the ordinary log rank test and the Lin-Wei (LW) test based on the marginal Cox proportional Hazards model with robust standard errors obtained from the sandwich estimator. Simulation results indicate that the ordinary log rank test over-inflates type I error, while the proposed unconditional likelihood ratio test has appropriate type I error and higher power than the LW test. The method is demonstrated in real examples from the Sorbinil Retinopathy Trial, and the Age-Related Macular Degeneration Study. Raw data from these two trials are provided.

[Guidelines for prevention and treatment of colorectal adenoma with integrated Chinese and western medicine].

The Guidelines for prevention and treatment of colorectal adenoma with integrated Chinese and western medicine are put forward by Nanjing University of Chinese Medicine and approved by China Association of Chinese Medicine. According to the formulation processes and methods of relevant clinical practice guidelines, the experts in clinical medicine and methodology were organized to discuss the key problems to be addressed in the clinical prevention and treatment of colorectal adenoma(CRA) and provided answers following the evidence-based medicine method, so as to provide guidance for clinical decision-making. CRA is the major precancerous disease of colorectal cancer. Although the prevention and treatment with integrated Chinese and western medicine have been applied to the clinical practice of CRA, there is still a lack of high-quality guidelines. Four basic questions, 15 clinical questions, and 10 outcome indicators were determined by literature research and Delphi questionnaire. The relevant randomized controlled trial(RCT) was retrieved from CNKI, Wanfang, VIP, SinoMed, PubMed, EMbase, Cochrane Library, Web of Science, and 2 clinical trial registries, and finally several RCTs meeting the inclusion criteria were included. The data extracted from the RCT was imported into RevMan 5.3 for evidence synthesis, and the evidence was evaluated based on the Grading of Recommendations, Assessment, Development, and Evaluations(GRADE). The final recommendations were formed by the nominal group method based on the evidence summary table. The guidelines involve the diagnosis, screening, treatment with integrated Chinese and western medicine, prevention, and follow-up of colorectal adenoma, providing options for the clinical prevention and treatment of CRA.

Group sequential design for randomized trials using "first hitting time" model.

Group sequential design (GSD) has become a popular choice in recent clinical trials as it improves trial efficiency by providing options for early termination. The implementation of traditional tests for survival analysis (eg, the log-rank test and the Cox proportional hazard (PH) model) in the GSD setting has been widely discussed. The PH assumption is required for conventional (sequential) design, it is, however, often violated in practice. As an alternative, some generalized tests have been proposed (eg, the Max-Combo test) and their efficacies have been established. In this article, we explore the application of a more flexible, "first hitting time" based threshold regression (TR) model to GSD. TR assumes that subjects' health status is a latent (unobservable) process, and the clinical event of interest occurs when the latent health process hits a pre-specified boundary. The simulation results supported our findings that, in most cases, this comparable new method can successfully control type I error while providing higher early stopping opportunities in the sequential design, even when non-proportional hazard presents.

Applying the RE-AIM framework to evaluate a holistic caregiver-centric hospital-to-home programme: a feasibility study on Carer Matters.

BACKGROUND: Prolonged caregiving of an older adult can cause family caregivers to be overwhelmed, potentially affecting the well-being of both the caregivers and their care-recipients. Carer Matters is a holistic hospital-to-home programme, centred on caregivers' needs as their care-recipients transit from hospital to home. The programme was piloted to support caregivers through caregivers needs assessment, tailored resources, tele-support, training courses, and community support network. This study aimed to examine the feasibility of Carer Matters in a tertiary hospital in Singapore. METHODS: This feasibility study was conducted on the pilot implementation from January to December 2021, during the Covid-19 pandemic. It adopted the Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) framework. The study highlighted quantitative data collected from key process indicators, such as number of caregivers screened, assessed on their needs and provided with assistance. Additionally, qualitative data was collected from in-depth interviews with 51 stakeholders involved in the implementation to examine their perspectives and experiences. These included family caregivers, clinician caregiver support nurses, hospital leaders and community partners. RESULTS: During the pilot, 550 caregivers were enrolled. All caregivers received educational resources when they completed the needs assessment, while 69 of them who reported high burden were given tele-support and 252 attended our caregiver training courses. Despite initial recruitment challenges and obstacles to adoption, stakeholders interviewed found Carer Matters to be effective in providing caregivers with emotional support, knowledge and skills that improved their caregiving abilities, and reduced their sense of isolation and caregiving stress. Among caregivers, the training courses were effective with majority of caregivers agreeing that the courses addressed their needs (99%) and improved their knowledge of the relevant disease conditions (97%). Programme maintenance considered among stakeholders included strategies such as multipronged approach in recruiting caregivers and inviting caregiver advocates to share their experiences. CONCLUSION: This feasibility study highlights that Carer Matters is a valuable component to the ecosystem of support for family caregivers and their care recipients. Carer Matters extends the current patient-centric care model to a more holistic post-discharge continuity of care for both caregivers and their care-recipients, improving and maintaining their overall well-being to better allow transition from hospital-to home. TRIAL REGISTRATION: Feasibility Study of Project Carer Matters for Family Caregivers of Persons with Dementia (NCT number: NCT05205135 ).

Accounting for delayed entry into observational studies and clinical trials: length-biased sampling and restricted mean survival time.

Individuals in many observational studies and clinical trials for chronic diseases are enrolled well after onset or diagnosis of their disease. Times to events of interest after enrollment are therefore residual or left-truncated event times. Individuals entering the studies have disease that has advanced to varying extents. Moreover, enrollment usually entails probability sampling of the study population. Finally, event times over a short to moderate time horizon are often of interest in these investigations, rather than more speculative and remote happenings that lie beyond the study period. This research report looks at the issue of delayed entry into these kinds of studies and trials. Time to event for an individual is modelled as a first hitting time of an event threshold by a latent disease process, which is taken to be a Wiener process. It is emphasized that recruitment into these studies often involves length-biased sampling. The requisite mathematics for this kind of sampling and delayed entry are presented, including explicit formulas needed for estimation and inference. Restricted mean survival time (RMST) is taken as the clinically relevant outcome measure. Exact parametric formulas for this measure are derived and presented. The results are extended to settings that involve study covariates using threshold regression methods. Methods adapted for clinical trials are presented. An extensive case illustration for a clinical trial setting is then presented to demonstrate the methods, the interpretation of results, and the harvesting of useful insights. The closing discussion covers a number of important issues and concepts.

Extraction of bioavailable phosphorus in soils and sediments using an ultrasonic washing machine.

For improving the management of watershed eutrophication, methods for measuring bioavailable phosphorus (BAP) are more important than measurements of total phosphorus (TP). BAP in particulate form (P-BAP) is an important substance that promotes eutrophication, especially during rainy seasons. Only a portion of particulate phosphorus (PP) is taken up by algae that contribute to eutrophication. Erosion and runoff associated with rainfall transport PP bound to sediments and soil particles to surface waters, thus increasing PP concentration. This research evaluated an extraction method using an ultrasonic washing machine for extraction time and frequency. Extraction at a frequency of 28-45 kHz and an extraction time of 1 min resulted in extracted P concentrations almost the same as concentrations extracted using conventional methods. This new method requires less time and is more efficient than conventional methods because it extracts P from multiple samples in a single step. Results indicate that extraction using an ultrasonic washing machine is a promising method for rapidly obtaining BAP from sediments and soil particles.

Correction to: "Getting Everyone on the Same Page": Interprofessional Team Training to Develop Shared Mental Models on Interprofessional Rounds.

This capsule commentary, Capsule Commentary on Liaw et al., "Getting everyone on the same page": interprofessional team training to develop shared mental models on interprofessional rounds," was to have accompanied the article, DOI: https://doi.org/10.1007/s11606-019-05320-z, which appeared in the December 2019 issue.

Order-restricted inference for clustered ROC data with application to fingerprint matching accuracy.

Receiver operating characteristic (ROC) curve is commonly used to evaluate and compare the accuracy of classification methods or markers. Estimating ROC curves has been an important problem in various fields including biometric recognition and diagnostic medicine. In real applications, classification markers are often developed under two or more ordered conditions, such that a natural stochastic ordering exists among the observations. Incorporating such a stochastic ordering into estimation can improve statistical efficiency (Davidov and Herman, 2012). In addition, clustered and correlated data arise when multiple measurements are gleaned from the same subject, making estimation of ROC curves complicated due to within-cluster correlations. In this article, we propose to model the ROC curve using a weighted empirical process to jointly account for the order constraint and within-cluster correlation structure. The algebraic properties of resulting summary statistics of the ROC curve such as its area and partial area are also studied. The algebraic expressions reduce to the ones by Davidov and Herman (2012) for independent observations. We derive asymptotic properties of the proposed order-restricted estimators and show that they have smaller mean-squared errors than the existing estimators. Simulation studies also demonstrate better performance of the newly proposed estimators over existing methods for finite samples. The proposed method is further exemplified with the fingerprint matching data from the National Institute of Standards and Technology Special Database 4.

Minimum 8-year follow-up of revision THA with severe femoral bone defects using extensively porous-coated stems and cortical strut allografts.

BACKGROUND: Revision total hip arthroplasty (THA) with severe femoral bone defects remains a major challenge. The purpose of this study is to report the minimum 8-year clinical and radiographic results of revision THA with severe femoral bone defects treated with extensively porous-coated stems and cortical strut allografts. METHODS: We retrospectively identified 44 patients diagnosed with Paprosky type III and IV femoral bone defects between January 2006 and July 2011. The exclusion criteria were patients not eligible for surgery, revised with extensively porous-coated stems alone, lost to follow-up and deceased. A total of 31 patients treated with extensively porous-coated stems and cortical strut allografts were finally included in this study. The degree of femoral bone defects was categorized as Paprosky type IIIA in 19 patients, type IIIB in 9 patients and type IV in 3 patients. The mean duration of follow-up was 11.0 ± 1.5 (range, 8.1-13.5) years. RESULTS: The mean Harris Hip Score improved significantly from 43.4 ± 10.5 points to 85.2 ± 6.6 points (P < 0.001). Similarly, WOMAC and SF-12 scores also significantly improved. Twenty-eight stems achieved stable bone ingrowth, two stems showed stable fibrous ingrowth, and one stem was radiologically unstable. Complete union and bridging between cortical strut allografts and host bone was achieved in all 31 patients. The femoral width was augmented with cortical strut allografts after revision surgery (an increase of 10.5 ± 0.5 mm) and showed a slight decrease of 2.5 ± 4.8 mm after the 10-year follow-up. Using re-revision for any reason as an endpoint, the Kaplan-Meier cumulative survival rate of the stem was 96.2% (95% confidence interval, 75.7-99.5%) at 10 years. CONCLUSION: Our data demonstrate that the use of extensively porous-coated stems combined with cortical strut allografts in revision THA with Paprosky type III and IV femoral bone defects can provide satisfactory clinical and radiographic outcomes with a minimum follow-up of 8 years.

Temperature-sensitive bone mesenchymal stem cells combined with mild hypothermia reduces neurological deficit in rats of severe traumatic brain injury.

BACKGROUND: To explore the combined influences of temperature-sensitive bone mesenchymal stem cells (tsBMSCs) and mild hypothermia (MH) on neurological function and glucose metabolism in rats with severe traumatic brain injury (TBI). METHODS: SD rats were randomly divided into sham, TBI, TBI + MH, TBI + BMSCs and TBI + MH +tsBMSCs groups. Then, the brain water content, serum-specific proteins (S100ß, NSE, LDH, and CK), and blood glucose at different time points were measured. Furthermore, GLUT-3 expression was detected by Western blotting, and apoptotic rate was determined by TUNEL staining. RESULTS: After TBI rat establishment, the brain injury resulted in significant increases in mNSS scores and brain water content, and upregulations in serum levels of S100ß, NSE, LDH and CK, and blood glucose, with the elevated cell apoptotic rate in the injured cortex. However, these changes were reversed by MH alone, BMSCs alone, or combination treatment of MH and tsBMSCs in varying degrees, and the combination treatment was superior to the treatment with BMSCs or MH alone. CONCLUSION: Combination therapy of tsBMSCs and MH can reduce the neuronal apoptosis in severe TBI rats, with the suppression of serum biomarkers and hyperglycemia, contributing to the recovery of neurological functions. ABBREVIATIONS: tsBMSCs: temperature-sensitive bone mesenchymal stem cells; MH: mild hypothermia; TBI: traumatic brain injury; mNSS: modified Neurological Severity Score.

Drug overdose mortality is associated with employment status and occupation in the National Longitudinal Mortality Study.

BACKGROUND: Since 1999, over 702,000 people in the US have died of a drug overdose, and the drug overdose death rate has increased from 6.2 to 21.8 per 100,000. Employment status and occupation may be important social determinants of overdose deaths. OBJECTIVES: Estimate the risk of drug overdose death by employment status and occupation, controlling for other social and demographic factors known to be associated with overdose deaths. METHODS: Proportional hazard models were used to study US adults in the National Longitudinal Mortality Study with baseline measurements taken in the early 2000s and up to 6 years of follow-up (n = 438,739, 53% female, 47% male). Comparisons were made between adults with different employment statuses (employed, unemployed, disabled, etc.) and occupations (sales, construction, service occupations, etc.). Models were adjusted for age, sex, race/ethnicity, education, income and marital status. RESULTS: Adults who were disabled (hazard ratio (HR) = 6.96 (95% CI = 6.81-7.12)), unemployed (HR = 4.20, 95% CI = 4.09-4.32) and retired (HR = 2.94, 95% CI = 2.87-3.00) were at higher risk of overdose death relative to those who were employed. By occupation, those working in service (HR = 2.05, 95% CI = 1.97-2.13); construction and extraction (HR = 1.69, 95% CI = 1.64-1.76); management, business and financial (HR = 1.39, 95% CI = 1.33-1.44); and installation, maintenance and repair (HR = 1.32, 95% CI = 1.25-1.40) occupations displayed higher risk relative to professional occupations. CONCLUSIONS: In a large national cohort followed prospectively for up to 6 years, several employment statuses and occupations are associated with overdose deaths, independent of a range of other factors. Efforts to prevent overdose deaths may benefit from focusing on these high-risk groups.

Active Transport of Membrane Components by Self-Organization of the Min Proteins.

Heterogeneous distribution of components in the biological membrane is critical in the process of cell polarization. However, little is known about the mechanisms that can generate and maintain the heterogeneous distribution of the membrane components. Here, we report that the propagating wave patterns of the bacterial Min proteins can impose steric pressure on the membrane, resulting in transport and directional accumulation of the component in the membrane. Therefore, the membrane component waves represent transport of the component in the membrane that is caused by the steric pressure gradient induced by the differential levels of binding and dissociation of the Min proteins in the propagating waves on the membrane surface. The diffusivity, majorly influenced by the membrane anchor of the component, and the repulsed ability, majorly influenced by the steric property of the membrane component, determine the differential spatial distribution of the membrane component. Thus, transportation of the membrane component by the Min proteins follows a simple physical principle, which resembles a linear peristaltic pumping process, to selectively segregate and maintain heterogeneous distribution of materials in the membrane. VIDEO ABSTRACT.