Efficient Synthesis of µ-A(BC)C Miktoarm Star Polymer Assemblies via Aqueous Photoinitiated Polymerization-Induced Self-Assembly.

In this study, green light-activated photoiniferter reversible addition-fragmentation chain transfer (RAFT) polymerization of glycerol methacrylate was performed using an ω,ω-heterodifunctional macro-RAFT agent. Because of the different RAFT controllability of two RAFT groups toward methacrylic monomers, only one RAFT group was activated under green light irradiation, leading to the formation of a diblock copolymer macro-RAFT agent with one RAFT group located at the chain end and the other RAFT group located between two blocks. The obtained diblock copolymer macro-RAFT agent was then used to mediate aqueous photoinitiated RAFT dispersion polymerization of diacetone acrylamide (DAAM), which formed µ-A(BC)C miktoarm star polymer assemblies with a diverse set of morphologies. Comparing with the ABC triblock copolymer, it was found that the architecture of the µ-A(BC)C miktoarm star polymer facilitated the formation of higher-order morphologies. Kinetic studies indicated that the aqueous photoinitiated RAFT dispersion polymerization exhibited ultrafast polymerization behavior, with quantitative monomer conversion being achieved within 5 min. Size exclusion chromatography analysis confirmed that good RAFT control was maintained during the polymerization. A morphological phase diagram for µ-A(BC)C miktoarm star polymer assemblies was constructed by varying the monomer concentration and the [DAAM]/[Macro-RAFT] ratio. We expect that this study not only develops an approach for the preparation of miktoarm star polymer assemblies but also provides mechanistic insights into the polymerization-induced self-assembly of nonlinear polymers.

Aqueous RAFT Dispersion Polymerization Mediated by an ω,ω-Macromolecular Chain Transfer Monomer: An Efficient Approach for Amphiphilic Branched Block Copolymers and the Assemblies.

Herein, an ω,ω-macromolecular chain transfer monomer (macro-CTM) containing a RAFT (reversible addition-fragmentation chain transfer) group and a methacryloyl group was synthesized and used to mediate photoinitiated RAFT dispersion polymerization of hydroxypropyl methacrylate (HPMA) in water. The macro-CTM undergoes a self-condensing vinyl polymerization (SCVP) mechanism under RAFT dispersion polymerization conditions, leading to the formation of amphiphilic branched block copolymers and the assemblies. Compared with RAFT solution polymerization, it was found that the SCVP process was promoted under RAFT dispersion polymerization conditions. Morphologies of branched block copolymer assemblies could be controlled by varying the monomer concentration and the [HPMA]/[macro-CTM] ratio. The branched block copolymer vesicles could be used as seeds for seeded RAFT emulsion polymerization, and framboidal vesicles were successfully obtained. Finally, degrees of branching of branched block copolymers could be further controlled by using a binary mixture of the macro-CTM and a linear macro-RAFT agent or a small molecule CTM. We believe that this study not only provides a versatile strategy for the preparation of branched block copolymer assemblies but also offers important insights into polymer synthesis via heterogeneous RAFT polymerization.

Grafting Block Copolymer Nanoparticles to a Surface via Aqueous Photoinduced Polymerization-induced Self-Assembly at Room Temperature.

The creation of well-defined surface nanostructures is important for a diverse set of applications such as cell adhesion, superhydrophobic coating, and lithography. In this study, we describe a robust bottom-up method for surface functionalization that involves surface-initiated reversible deactivation radical polymerization (RDRP) and the grafting of block copolymer nanoparticles to material surfaces via aqueous photoinduced polymerization-induced self-assembly (photo-PISA) at room temperature. Using silica nanoparticles as a model substrate, colloidal mesoscale hybrid assemblies with various morphologies were successfully prepared. The morphologies can be easily tuned by changing the lengths of macromolecular chain transfer agents and parameters of the silica nanoparticles. The surface-initiated photo-PISA approach can also be employed for other large-scale substrates such as silicon wafer. Taking advantage of mild reaction conditions of this method (room temperature, aqueous medium, and visible light), enzymatic deoxygenation was introduced to develop oxygen-tolerant surface-initiated photo-PISA that can fabricate well-defined nanostructures on large-scale substrates under open-to-air conditions.

Exploiting the Monomer-Feeding Mechanism of RAFT Emulsion Polymerization for Polymerization-Induced Self-Assembly of Asymmetric Divinyl Monomers.

We exploited the monomer-feeding mechanism of reversible addition-fragmentation chain transfer (RAFT) emulsion polymerization to achieve the successful polymerization-induced self-assembly (PISA) of asymmetric divinyl monomers. Colloidally stable cross-linked block copolymer nanoparticles with various morphologies, such as vesicles, were directly prepared at high solids. Morphologies of the cross-linked block copolymer nanoparticles could be controlled by varying the monomer concentration, degree of polymerization (DP) of the core-forming block, and length of the macro-RAFT agent. X-ray photoelectron spectroscopy (XPS) characterization confirmed the presence of unreacted vinyl groups within the obtained block copolymer nanoparticles, providing a landscape for further functionalization via thiol-ene chemistry. Finally, the obtained block copolymer nanoparticles were employed as additives to tune the mechanical properties of hydrogels. We expect that this study not only offers considerable opportunities for the preparation of well-defined cross-linked block copolymer nanoparticles, but also provides important insights into the controlled polymerization of multivinyl monomers.

Seeded RAFT Polymerization-Induced Self-assembly: Recent Advances and Future Opportunities.

Over the past decade, polymerization-induced self-assembly (PISA) has fully proved its versatility for scale-up production of block copolymer nanoparticles with tunable sizes and morphologies; yet, there are still some limitations. Recently, seeded PISA approaches combing PISA with heterogeneous seeded polymerizations have been greatly explored and are expected to overcome the limitations of traditional PISA. In this review, recent advances in seeded PISA that have expanded new horizons for PISA are highlighted including i) general considerations for seeded PISA (e.g., kinetics, the preparation of seeds, the selection of monomers), ii) morphological evolution induced by seeded PISA (e.g., from corona-shell-core nanoparticles to vesicles, vesicles-to-toroid, disassembly of vesicles into nanospheres), and iii) various well-defined nanoparticles with hierarchical and sophisticated morphologies (e.g., multicompartment micelles, porous vesicles, framboidal vesicles, AXn -type colloidal molecules). Finally, new insights into seeded PISA and future perspectives are proposed.

High-Flow Nasal Cannula Oxygen Therapy versus Non-Invasive Ventilation in AIDS Patients with Acute Respiratory Failure: A Randomized Controlled Trial.

BACKGROUND: Acute respiratory failure (ARF) remains the most common diagnosis for intensive care unit (ICU) admission in acquired immunodeficiency syndrome (AIDS) patients. METHODS: We conducted a single-center, prospective, open-labeled, randomized controlled trial at the ICU, Beijing Ditan Hospital, China. AIDS patients with ARF were enrolled and randomly assigned in a 1:1 ratio to receive either high-flow nasal cannula (HFNC) oxygen therapy or non-invasive ventilation (NIV) immediately after randomization. The primary outcome was the need for endotracheal intubation on day 28. RESULTS: 120 AIDS patients were enrolled and 56 patients in the HFNC group and 57 patients in the NIV group after secondary exclusion. Pneumocystis pneumonia (PCP) was the main etiology for ARF (94.7%). The intubation rates on day 28 were similar to HFNC and NIV (28.6% vs. 35.1%, p = 0.457). Kaplan-Meier curves showed no statistical difference in cumulative intubation rates between the two groups (log-rank test 0.401, p = 0.527). The number of airway care interventions in the HFNC group was fewer than in the NIV group (6 (5-7) vs. 8 (6-9), p < 0.001). The rate of intolerance in the HFNC group was lower than in the NIV group (1.8% vs. 14.0%, p = 0.032). The VAS scores of device discomfort in the HFNC group were lower than that in the NIV group at 2 h (4 (4-5) vs. 5 (4-7), p = 0.042) and at 24 h (4 (3-4) vs. 4 (3-6), p = 0.036). The respiratory rate in the HFNC group was lower than that in the NIV group at 24 h (25 ± 4/min vs. 27 ± 5/min, p = 0.041). CONCLUSIONS: Among AIDS patients with ARF, there was no statistical significance of the intubation rate between HFNC and NIV. HFNC had better tolerance and device comfort, fewer airway care interventions, and a lower respiratory rate than NIV. CLINICAL TRIAL NUMBER: Chictr.org (ChiCTR1900022241).

Extracorporeal membrane oxygenation in curing a young man after modified Fontan operation: A case report.

BACKGROUND: The Fontan operation is the only treatment option to change the anatomy of the heart and help improve patients' hemodynamics. After successful operation, patients typically recover the ability to engage in general physical activity. As a better ventilatory strategy, extracorporeal membrane oxygenation (ECMO) provides gas exchange via an extracorporeal circuit, and is increasingly being used to improve respiratory and circulatory function. After the modified Fontan operation, circulation is different from that of patients who are not subjected to the procedure. This paper describe a successful case using ECMO in curing influenza A infection in a young man, who was diagnosed with Tausing-Bing syndrome and underwent Fontan operation 13 years ago. The special cardiac structure and circulatory characteristics are explored in this case. CASE SUMMARY: We report a successful case using ECMO in curing influenza A infection in a 23-year-old man, who was diagnosed with Tausing-Bing syndrome and underwent Fontan operation 13 years ago. The man was admitted to the intensive care unit with severe acute respiratory distress syndrome as a result of influenza A infection. He was initially treated by veno-venous (VV) ECMO, which was switched to veno-venous-arterial ECMO (VVA ECMO) 5 d later. As circulation and respiratory function gradually improved, the VVA ECMO equipment was removed on May 1, 2018. The patient was successfully withdrawn from artificial ventilation on May 28, 2018 and then discharged from hospital on May 30, 2018. CONCLUSION: After the modified Fontan operation, circulation is different compared with that of patients who are not subjected to the procedure. There are certainly many differences between them when they receive the treatment of ECMO. Due to the special cardiac structure and circulatory characteristics, an individualized liquid management strategy is necessary and it might be better for them to choose an active circulation support earlier.

Linear and Star Block Copolymer Nanoparticles Prepared by Heterogeneous RAFT Polymerization Using an ω,ω-Heterodifunctional Macro-RAFT Agent.

Herein, an ω,ω-heterodifunctional macromolecular reversible addition-fragmentation chain transfer (macro-RAFT) agent containing two different RAFT end groups was synthesized and employed to mediate aqueous photoinitiated RAFT dispersion polymerization of a methacrylic monomer. Because of the different RAFT controllability of two RAFT end groups toward methacrylic monomers, the RAFT end group with good controllability dominated the polymerization while the other RAFT end group with poor controllability was unreacted, leading to the formation of linear block copolymers. Because of the unique structure of the linear block copolymers, a diverse set of block copolymer nanoparticles with rich RAFT groups at the interface of the hydrophilic corona/the hydrophobic core were successfully prepared. Finally, µ-A(BC)C miktoarm star block copolymer nanoparticles were prepared by RAFT seeded emulsion polymerization of an acrylic monomer, which enables the further morphological control over polymer nanoparticles. We believe that the utilization of an ω,ω-heterodifunctional macro-RAFT agent in heterogeneous RAFT polymerization will offer considerable opportunities for the rational synthesis of well-defined molecular architectures and polymer nanoparticles.

Exploiting Wavelength Orthogonality in Photoinitiated RAFT Dispersion Polymerization and Photografting for Monodisperse Surface-Functional Polymeric Microspheres.

We report a strategy toward surface-functional polymeric microspheres using a wavelength orthogonality technique that employs photoinitiated reversible addition-fragmentation chain transfer (RAFT) dispersion polymerization and the subsequent photografting under different wavelengths of light. Initial screening of reaction conditions indicated photoreactive polymeric microsphere with uniform sizes could be prepared by using photoinitiator-functionalized macro-RAFT agents under purple light irradiation. Photoreactive polymeric microspheres allowed photografting polymerizations under UV light irradiation, and we further demonstrated the broad scope of this method by photografting acrylamide, acrylic, and methacrylic monomers. Finally, carboxyl-functionalized polymeric microspheres with an exceptional high number of carboxyl groups were successfully prepared by this technique, which permitted extensive surface bioconjugation of model proteins (e.g., streptavidin). This method should expand the capabilities of RAFT dispersion polymerization to afford diverse surface-functional polymeric microspheres for some specific applications.

High-Performance Dielectric Elastomer Nanogenerator for Efficient Energy Harvesting and Sensing via Alternative Current Method.

Soft, low-cost, high-performance generators are highly desirable for harvesting ambient low frequency mechanical energy. Here, a dielectric elastomer nanogenerator (DENG) is reported, which consists of a dielectric elastomer capacitor, an electret electrostatic voltage source, and a charge pump circuit. Under biaxial stretching, DENG can convert tensile mechanical energy into electrical power without any external power supply. Different from traditional DEG with the charge outward transfer in direct current (DC), the DENG works based on shuttle movement of internal charges in an alternating current (AC). Through alternating current (AC) method, the charge density of the DENG can reach 26 mC m-2 per mechanical cycle, as well as energy density of up to 140 mJ g-1 . Due to the all-solid-state structure without air gap, the DENG is capable of working stably under different ambient humidity (20 RH%-100 RH%). To demonstrate the applications, a water wave harvester based on the DENG is constructed. The integrated device powers a sensing communication module for self-powered remote weather monitoring, showing the potential application in ocean wave energy harvesting.

Block Copolymer Vesicles with Tunable Membrane Thicknesses and Compositions Prepared by Aqueous Seeded Photoinitiated Polymerization-Induced Self-Assembly at Room Temperature.

Block copolymer vesicles with diverse functionalities and intrinsic hollow structures have received considerable attention due to their broad applications in biomedical fields, including drug delivery, bioimaging, theranostics, gene therapy, etc. However, efficient preparation of block copolymer vesicles with tunable membrane thicknesses and compositions under mild conditions is still a challenge. Herein, we report an aqueous seeded photoinitiated polymerization-induced self-assembly (photo-PISA) for the precise preparation of block copolymer vesicles at room temperature. By changing the total degree of polymerization (DP) of the hydrophobic block in seeded photo-PISA, one can easily tune the membrane thickness without compromising the morphology of vesicles. Moreover, by adding different comonomers such as hydrophobic monomers, hydrophilic monomers, and cross-linkers into seeded photo-PISA, vesicles with different compositions could be prepared without compromising the morphology and colloidal stability. Polymerization kinetics show that seeded photo-PISA can skip the step of in situ self-assembly with a short homogeneous polymerization stage being observed. To demonstrate potential biological applications, enzymatic nanoreactors were constructed by loading horseradish peroxidase (HRP) inside vesicles via seeded photo-PISA. The enzymatic properties of these nanoreactors could be easily regulated by changing the membrane thickness and hydrophobicity. It is expected that this method can provide a facile platform for the precise preparation of block copolymer vesicles that may find applications in different fields.

Simultaneous Synthesis and Self-Assembly of Bottlebrush Block Copolymers at Room Temperature via Photoinitiated RAFT Dispersion Polymerization.

Bottlebrush polymers exhibiting unique properties have attracted considerable attention for applications in many research areas. Herein, the first simultaneous synthesis and self-assembly of bottlebrush block copolymers at room temperature via photoinitiated polymerization-induced self-assembly (photo-PISA) using multifunctional macromolecular chain transfer agents (macro-CTAs) is reported. Comparing with linear block copolymers, the bottlebrush block copolymers can promote the formation of higher-order morphologies (e.g., vesicles) when targeting similar degrees of polymerization (DPs). Moreover, a higher polymerization rate is observed in the case of bottlebrush block copolymers. Gel permeation chromatography (GPC) analysis shows that good polymerization control is maintained when synthesizing bottlebrush block copolymers by photo-PISA. Finally, the obtained bottlebrush block copolymer vesicles are used as seeds for further chain extension and multicompartment nanoparticles with a sponge internal structure are formed. It is expected that this study will not only expand polymer architectures employed in PISA, but also provide a new strategy to synthesize polymer nanoparticles with unique structures.

A Stretchable Expanded Polytetrafluorethylene-Silicone Elastomer Composite Electret for Wearable Sensor.

Soaring developments in wearable electronics raise an urgent need for stretchable electrets. However, achieving soft electrets simultaneously possessing excellent stretchability, longevity, and high charge density is still challenging. Herein, a facile approach is proposed to prepare an all-polymer hybrid composite electret based on the coupling of elastomer and ePTFE membrane. The composite electrets are fabricated via a facile casting and thermal curing process. The obtained soft composite electrets exhibit constantly high surface potential (-0.38 kV) over a long time (30 days), large strain (450%), low hysteresis, and excellent durability (15,000 cycles). To demonstrate the applications, the stretchable electret is utilized to assemble a self-powered flexible sensor based on the electrostatic induction effect for the monitoring of human activities. Additionally, output signals in the pressure mode almost two orders of magnitude larger than those in the strain mode are observed and the sensing mechanism in each mode is investigated.

Expanding the Scope of Polymerization-Induced Self-Assembly: Recent Advances and New Horizons.

Over the past decade or so, polymerization-induced self-assembly (PISA) has become a versatile method for rational preparation of concentrated block copolymer nanoparticles with a diverse set of morphologies. Much of the PISA literature has focused on the preparation of well-defined linear block copolymers by using linear macromolecular chain transfer agents (macro-CTAs) with high chain transfer constants. In this review, a recent process is highlighted from an unusual angle that has expanded the scope of PISA including i) synthesis of block copolymers with nonlinear architectures (e.g., star block copolymer, branched block copolymer) by PISA, ii) in situ synthesis of blends of polymers by PISA, and iii) utilization of macro-CTAs with low chain transfer constants in PISA. By highlighting these important examples, new insights into the research of PISA and future impact these methods will have on polymer and colloid synthesis are provided.

COVID-19 Cases from the First Local Outbreak of the SARS-CoV-2 B.1.1.7 Variant in China May Present More Serious Clinical Features: A Prospective, Comparative Cohort Study.

The SARS-CoV-2 B.1.1.7 variant has increased sharply in numbers worldwide and is reported to be more contagious than the nonvariant. Little is known regarding the detailed clinical features of B.1.1.7 variant infection. Data on 74 COVID-19 cases from two outbreaks in two districts of Beijing, China were extracted from a cloud database, including 41 cases from Shunyi District (Shunyi B.1.470 group) and 33 from Daxing (Daxing B.1.1.7 group) from December 25, 2020 to January 17, 2021. We conducted a comparison of the clinical characteristics. Seven clinical indicators of the Daxing B.1.1.7 group were significantly higher than those of the Shunyi group, including the proportion with fever over 38°C, the levels of C-reactive protein (CRP), serum amyloid A (SAA), creatine kinase (CK), d-dimer (DD), and CD4+ T lymphocytes (CD4+ T), and the proportion with ground-glass opacity (GGO) in the lung (P values of ≤0.05). After adjusting for age, B.1.1.7 variant infection was a risk factor for elevated CRP (P = 0·045), SAA (P = 0·011), CK (P = 0·034), and CD4+ T (P = 0.029) and for the presence of GGO (P = 0.005). The median threshold cycle (CT) value of reverse transcriptase quantitative PCR (RT-qPCR) tests of the N gene target in the Daxing B.1.1.7 group was significantly lower (P = 0.036) than that in the Shunyi B.1.470 group. Clinical features, including a more serious inflammatory response, pneumonia, and a possibly higher viral load, were detected in the cases infected with B.1.1.7 SARS-CoV-2. The B.1.1.7 variant may have increased pathogenicity. IMPORTANCE The SARS-CoV-2 B.1.1.7 variant, which was first identified in the United Kingdom, has increased sharply in numbers worldwide and was reported to be more contagious than the nonvariant. To our knowledge, no studies investigating the detailed clinical features of COVID-19 cases infected with the B.1.1.7 variant have been published. Local epidemics have rarely occurred in China, but occasionally, a small clustered outbreak triggered by an imported SARS-CoV-2 strain with only one chain of transmission could happen. From late 2020 to early 2021, two clustered COVID-19 outbreaks occurred in Beijing, one of which was caused by the B.1.1.7 variant. The COVID-19 patients from the two outbreaks received similar clinical tests, diagnoses, and treatments. We found that the B.1.1.7 variant infection could lead to a more serious inflammatory response, acute response process, more severe pneumonia, and probably higher viral loads. This therefore implies that the B.1.1.7 variant may have increased pathogenicity.

How the Reactive End Group of Macro-RAFT Agent Affects RAFT-Mediated Emulsion Polymerization-Induced Self-Assembly.

Polymerization-induced self-assembly via reversible addition-fragmentation chain transfer (RAFT)-mediated emulsion polymerization is an emerging method in which macro-RAFT agents are chain extended with hydrophobic monomers in water to form block copolymer nano-objects. However, almost all RAFT-mediated emulsion polymerizations are limited to AB diblock copolymers by using monofunctional macro-RAFT agents with non-reactive end groups. In this study, the first investigation on how the reactive end group of macro-RAFT agent affects RAFT-mediated emulsion polymerization is reported. Three macro-RAFT agents with different end groups are synthesized and employed in RAFT-mediated emulsion polymerization. Effects of end groups on morphologies of block copolymer nano-objects and polymerization process are studied. Block copolymer nano-objects prepared by using an asymmetric difunctional macro-RAFT agent can be functionalized by further chain extension on the surface. It is expected that the current study will not only expand the scope of RAFT-mediated emulsion polymerization, but also provide a novel strategy to prepare functional polymer nanoparticles.

One-Step Preparation of Thermo-Responsive Poly(N-isopropylacrylamide)-Based Block Copolymer Nanoparticles by Aqueous Photoinitiated Polymerization-Induced Self-Assembly.

Poly(N-isopropylacrylamide) (PNIPAM) is an important thermo-responsive polymer that finds applications in many areas. However, the preparation of PNIPAM-based block copolymer nanoparticles with higher-order morphologies at high solids is challenging. Herein, aqueous photoinitiated polymerization-induced self-assembly (photo-PISA) of N-isopropylacrylamide (NIPAM) using an asymmetrical cross-linker is developed for one-step preparation of PNIPAM-based block copolymer nanoparticles with various morphologies (spheres, worms, and vesicles). It is demonstrated that reaction temperature has a great effect on both polymerization kinetics and morphologies of block copolymer nanoparticles. Reversible addition-fragmentation chain transfer (RAFT) reactive groups embedded inside the PNIPAM core provide a landscape for further functionalization. PNIPAM-based block copolymer nanoparticles with different surface properties are prepared by seeded photo-PISA at room temperature. Finally, these block copolymer nanoparticles are also used as additives to tune mechanical properties of hydrogels via covalent cross-linking.

Case Report: Identification of SARS-CoV-2 in Cerebrospinal Fluid by Ultrahigh-Depth Sequencing in a Patient With Coronavirus Disease 2019 and Neurological Dysfunction.

We reported that the complete genome sequence of SARS-Coronavirus-2 (SARS-CoV-2) was obtained from a cerebrospinal fluid (CSF) sample by ultrahigh-depth sequencing. Fourteen days after onset, seizures, maxillofacial convulsions, intractable hiccups and a significant increase in intracranial pressure developed in an adult coronavirus disease 2019 patient. The complete genome sequence of SARS-CoV-2 obtained from the cerebrospinal fluid indicates that SARS-CoV-2 can invade the central nervous system. In future, along with nervous system assessment, the pathogen genome detection and other indicators are needed for studying possible nervous system infection of SARS-CoV-2.

Preparation of Block Copolymer Nano-Objects with Embedded ß-Ketoester Functional Groups by Photoinitiated RAFT Dispersion Polymerization.

Herein, a photoinitiated reversible addition-fragmentation chain transfer (RAFT) dispersion polymerization of 2-(acetoacetoxy)ethyl methacrylate (AEMA) in ethanol/water at room temperature for in situ preparation of ß-ketoester-functionalized block copolymer nano-objects is reported. AEMA is also copolymerized with isobornyl methacrylate (IBOMA) to improve the colloidal stability of PIBOMA-based block copolymer nano-objects prepared by photoinitiated RAFT dispersion polymerization at low temperatures. A series of P(IBOMA-stat-AEMA)-based block copolymer nano-objects are prepared by changing reaction parameters. Finally, lanthanide-doped block copolymer nano-objects with luminescent and magnetic properties are also prepared based on the complexation of various lanthanide ions with the ß-ketoester group. It is expected that the current study will provide a facile platform for the in situ preparation of ß-ketoester-functionalized block copolymer nano-objects with different morphologies for specific applications.