Directed Self-Assembly by Sparsely Prepatterned Substrates with Self-Responsive Polymer Brushes.

The guiding pattern in the chemoepitaxially directed self-assembly (DSA) of block copolymers is often fabricated by periodically functionalizing homogeneously random copolymer brushes tethered on a substrate. The prepatterned copolymer brushes constitute a soft penetrable surface, and their two components can in principle locally segregate in response to the overlying self-assembly process of block copolymers. To reveal how the self-responsive behavior of the copolymer brushes affects the directing effect, we develop a dissipative particle dynamics model to explicitly include the prepatterned polymer brushes and implement it to simulate the DSA of a cylinder-forming diblock copolymer melt on the sparse pattern of polymer brushes. Through large-scale dynamic simulations, we identify the windows of the content of the random copolymer, the film thickness, and the diameter of the patterned spot, for the formation of perfectly ordered hexagonal patterns composed of perpendicular cylinders. Our dynamic simulations reveal that the random copolymer brushes grafted on the unpatterned area exhibit a remarkable self-responsive ability with respect to the self-assembly of the diblock copolymers overlying them, which may widen the effective window of the content of the random copolymer. Within the processing windows of these key parameters, defect-free patterns are successfully achieved both in simulations and in experiments with sizes as large as a few micrometers for 4-fold density multiplications. This work demonstrates that highly efficient computer simulations based on an effective model can provide helpful guidance for experiments to optimize the critical parameters and even may promote the application of DSA.

MicroRNA-302c-3p inhibits endothelial cell pyroptosis via directly targeting NOD-, LRR- and pyrin domain-containing protein 3 in atherosclerosis.

Inflammation and endothelial dysfunction are important participants and drivers in atherosclerosis. NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome activation and the resulting pyroptosis are involved in the initiation and vicious circle of chronic inflammation, thus playing an indispensable role in atherosclerosis. Accordingly, blocking the activation of NLRP3 inflammasome may be a promising treatment strategy to blunt the progression of atherosclerosis. In this study, it was demonstrated that miR-302c-3p exerted anti-pyroptosis effects by directly targeting NLRP3 in vivo and in vitro. In brief, the expression of miR-302c-3p was down-regulated whereas the expression of NLRP3 was up-regulated in human plaques and in vitro pyroptosis model of endothelial cells. Overexpression of miR-302c-3p suppressed endothelial cell pyroptosis by targeting specific sites of NLRP3. By comparison, down-regulation of endogenous miR-302c-3p led to the opposite results, which were reversed by silencing the expression of NLRP3. Finally, the up-regulation of miR-302c-3p inhibited the inflammation and pyroptosis of atherosclerosis mouse model. In conclusion, miR-302c-3p may be a powerful and attractive target for suppressing endothelial inflammation and pyroptosis, providing a novel strategy for preventing or alleviating the progression of atherosclerosis.

Transmission Potential of Asymptomatic and Paucisymptomatic Severe Acute Respiratory Syndrome Coronavirus 2 Infections: A 3-Family Cluster Study in China.

Data concerning the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in asymptomatic and paucisymptomatic patients are lacking. We report a 3-family cluster of infections involving asymptomatic and paucisymptomatic transmission. Eight of 15 (53%) members from 3 families were confirmed with SARS-CoV-2 infection. Of 8 patients, 3 were asymptomatic and 1 was paucisymptomatic. An asymptomatic mother transmitted the virus to her son, and a paucisymptomatic father transmitted the virus to his 3-month-old daughter. SARS-CoV-2 was detected in the environment of 1 household. The complete genomes of SARS-CoV-2 from the patients were > 99.9% identical and were clustered with other SARS-CoV-2 sequences reported from China and other countries.

Directed Self-Assembly of Polystyrene-b-poly(propylene carbonate) on Chemical Patterns via Thermal Annealing for Next Generation Lithography.

Directed self-assembly (DSA) of block copolymers (BCPs) combines advantages of conventional photolithography and polymeric materials and shows competence in semiconductors and data storage applications. Driven by the more integrated, much smaller and higher performance of the electronics, however, the industry standard polystyrene-block-poly(methyl methacrylate) (PS-b-PMMA) in DSA strategy cannot meet the rapid development of lithography technology because its intrinsic limited Flory-Huggins interaction parameter (χ). Despite hundreds of block copolymers have been developed, these BCPs systems are usually subject to a trade-off between high χ and thermal treatment, resulting in incompatibility with the current nanomanufacturing fab processes. Here we discover that polystyrene-b-poly(propylene carbonate) (PS-b-PPC) is well qualified to fill key positions on DSA strategy for the next-generation lithography. The estimated χ-value for PS-b-PPC is 0.079, that is, two times greater than PS-b-PMMA (χ = 0.029 at 150 °C), while processing the ability to form perpendicular sub-10 nm morphologies (cylinder and lamellae) via the industry preferred thermal-treatment. DSA of lamellae forming PS-b-PPC on chemoepitaxial density multiplication demonstrates successful sub-10 nm long-range order features on large-area patterning for nanofabrication. Pattern transfer to the silicon substrate through industrial sequential infiltration synthesis is also implemented successfully. Compared with the previously reported methods to orientation control BCPs with high χ-value (including solvent annealing, neutral top-coats, and chemical modification), the easy preparation, high χ value, and etch selectivity while enduring thermal treatment demonstrates PS-b-PPC as a rare and valuable candidate for advancing the field of nanolithography.

Directed self-assembly of solvent-vapor-induced non-bulk block copolymer morphologies on nanopatterned substrates.

We report a study on directed self-assembly (DSA) with solvent annealing to induce the formation of non-bulk block copolymer microdomains on chemical patterns. Ultrathin films of symmetric polystyrene-block-poly(methyl methacrylate) (PS-b-PMMA) display morphologies of PMMA dots, stripes, and PS hexagons with increasing exposure time to acetone vapor, a PMMA-selective solvent. All three nanostructures form long-range-ordered and registered arrays on striped chemical patterns with periods (LS) commensurate to the solvated PS-b-PMMA microdomain period (L0,s). Solvent annealing is shown to facilitate DSA on non-regular chemical patterns, on which the local periods are incommensurate to L0,s. DSA with feature density multiplication, via solvent annealing, is also demonstrated.

Four-Arm δ-Ornithine-Based Polypeptoids Resensitize Voriconazole against Azole-Resistant C. albicans.

Worldwide Candida albicans infections cause a huge burden in healthcare and the efficacy of traditional antifungals is diminished because of the rapid development of antifungal resistance. It is necessary to develop new antifungals or new strategies to make multidrug-resistant (MDR) C. albicans to resensitize to existing antifungal drugs. In this work, a series of 4-arm polypeptoids (FAPs) were synthesized through grafting linear ε-l-lysine or δ-ornithine-based oligopeptides to a trimeric lysine core. The most potent 4R-O7 exhibited excellent activities toward three sensitive and two MDR C. albicans strains with MIC values as low as 24-48 µg/mL (vs 375 µg/mL for ε-polylysine, ε-PL). The mechanism studies revealed that 4R-O7 penetrated the cell membrane and generated ROS to kill cells. 4R-O7 exhibited a synergistic effect (FICI < 0.5) with voriconazole (VOR) and also assisted VOR to restore its efficacy to MDR C. albicans. In addition, the combined use of 4R-O7 and VOR significantly improved the elimination efficacy of mature C. albicans biofilms and enhanced the potency in a mouse subcutaneous C. albicans infection model.

Manipulating the processing window of directed self-assembly in contact hole shrinking with binary block copolymer/homopolymer blending.

Directed self-assembly (DSA) lithography has demonstrated significant potential in fabricating integrated circuits. However, DSA encounters limited processing windows due to the requirement for precise matching between the period of block copolymers (BCPs) and graphoepitaxy templates. We propose a binary BCP/homopolymer blending strategy to manipulate the self-assembly behavior and the processing window of graphoepitaxy DSA in contact hole shrinking. By carefully tailoring the blending rates of poly(methyl methacrylate) (PMMA) with different molecular weights in cylindrical polystyrene-b-poly(methyl methacrylate) (PS-b-PMMA), we manipulate the period and morphology of BCP/homopolymer self-assembly. Specifically, we employ BCP/homopolymer blending to fine-tune the critical dimension (CD) of contact holes with PS-affined topographical templates. Subsequent pattern transferring is achieved by selectively etching defect-free shrinkable cylinders as hard masks. Furthermore, self-consistent field theory (SCFT) simulation was employed to explore the self-assembly of BCP/homopolymer blending in confined cylindrical space and the results were in good consistency with the experimental results.

In situ metallization of patterned polymer brushes created by molecular transfer print and fill.

A chemical pattern consisting of end-grafted polystyrene brushes (20 nm lines on a 40 nm pitch) on the native oxide of silicon wafers was defined by molecular transfer printing from assembled block co-polymer films. End-grafted hydroxyl-terminated poly(2-vinyl pyridine) brushes were selectively deposited in the interspatial regions. The poly(2-vinyl pyridine) regions selectively sequester acidic HAuCl4 from solution and form arrays of small Au nanoparticles upon exposure to oxygen plasma within the confines of the macromolecular brush layer. This print and fill process to pattern polymer brushes is a generalizable strategy to create functional chemical surface patterns.

Multi-arm ε-polylysines exhibit broad-spectrum antifungal activities against Candida species.

Invasive fungal infections pose a crucial threat to public health and are an under-recognized component of antimicrobial resistance, which is an emerging crisis worldwide. Here we designed and synthesized a panel of multi-arm ε-polylysines (ε-mPLs, nR-Km) with a precise number of n = 3-6 arms of ε-oligo(L-lysine)s and a precise arm length of m = 3-7 ε-lysine residues. ε-mPLs have good biocompatibility and exhibited broad-spectrum antifungal activities towards Aspergillus, Mucorales and Candida species, and their antifungal activities increased with residue arm length. Among these ε-mPLs, 3R-K7 showed high antifungal activity against C. albicans with a MIC value of as low as 24 µg mL-1 (only 1/16th that of ε-PL) and also exhibited similar antifungal activity towards the clinically isolated multi-drug resistant (MDR) C. albicans strain. Furthermore, 3R-K7 could inhibit the formation of C. albicans biofilms and kill the cells within mature C. albicans biofilms. Mechanistic studies proved that 3R-K7 killed fungal cells by entering the cells to generate reactive oxygen species (ROS) and induce cell apoptosis. An in vivo study showed that 3R-K7 significantly increased the survival rate of mice in a systemic murine candidiasis model, demonstrating that ε-mPL has great potential as a new antifungal agent.

Nonleaching Antimicrobial Cotton Fabrics Finished with Hyperbranched Polylysine.

The choice of the antimicrobial agent and finishing process is very important for the activity, durability, and safety of antimicrobial fabrics. Here, a novel antimicrobial cotton fabric (HPL-CF) was constructed by covalently bonding an antimicrobial agent, hyperbranched polylysine (HPL), onto the surface of a cotton fabric (CF) pretreated with a silane coupling agent, 3-chloropropyltrimethoxysilane (CPTMS). The multiple amino groups contained in the periphery of HPL make it possible to react with the CF to form multiple bonds, which is beneficial to improve the durability and safety of HPL-CFs. The obtained HPL-CFs exhibited excellent antimicrobial activities against Escherichia coli (E. coli, Gram-negative bacteria), Staphylococcus aureus (S. aureus, Gram-positive bacteria), and Candida albicans (C. albicans, fungi) even when the CF was treated with HPL solution at the concentration of 0.5 wt %. HPL2.0-CFs maintained 98, >99, and >99% of antimicrobial ratios for E. coli, S. aureus, and C. albicans, respectively, after 50 equiv of domestic laundering cycles, surpassing the requirements of the AAA class. The halo method, cell compatibility, and skin irritation assays all prove the fine safety of HPL-CFs. This work demonstrates the great advantages of applying HPL in the antimicrobial finishing of fabrics.

Room-temperature ferromagnetic CoSe2nanoplates synthesized by chemical vapor deposition.

Among novel two-dimensional materials, transition metal dichalcogenides (TMDs) with 3dmagnetic elements have been extensively researched owing to their unique magnetic, electric, and photoelectric properties. As an important member of TMDs, CoSe2is an interesting material with controversial magnetic properties, hitherto there are few reports related to the magnetism of CoSe2materials. Here, we report the synthesis of CoSe2nanoplates on Al2O3substrates by chemical vapor deposition (CVD). The CVD-grown CoSe2nanoplates exhibit three typical morphologies (regular hexagonal, hexagonal, and pentagonal shapes) and their lateral sizes and thickness of CoSe2nanoplates can reach up to hundreds of microns and several hundred nanometers, respectively. The electric-transport measurement shows a metallic feature of CoSe2nanoplates. Furthermore, the slanted hysteresis loop and nonzero remnant magnetization of the CoSe2nanoplates confirm the ferromagnetism in the temperature range of 5-400 K. This work provides a novel platform for designing CoSe2-based spintronic devices and studying related magnetic mechanisms.

Intercity spread of echovirus 6 in Shandong Province, China: application of environmental surveillance in tracing circulating enteroviruses.

Environmental surveillance is an effective approach in investigating circulating enteroviruses and had been conducted in the cities of Jinan and Linyi since February 2008 and April 2010, respectively. This study analyzed 46 sewage samples collected in the two cities in 2011 and found that echovirus 6 (E6) was the predominant serotype, with 134 isolates (65 in Jinan and 69 in Linyi) from 23 (50%) samples. This differs from the 2010 data that found 29 E6 isolates in Jinan and only 3 in Linyi. Phylogenetic analysis of the VP1 coding region showed that all environmental E6 samples from 2008 to 2011 (n = 167) segregated into two lineages and revealed an increase in VP1 gene diversity in 2011, suggesting that the increased number of E6 detections reflects a real epidemic in the two cities. Most Linyi isolates (n = 61, or 88%) in 2011 segregated into sublineage 1a, together with 18 Jinan isolates in 2011. Interestingly, the ancestral VP1 sequence of sublineage 1a inferred using the maximum-likelihood method had 100% identity with the sequence of one environmental isolate from Jinan in August 2010, suggesting an intercity spread from Jinan to Linyi. By Bayesian phylodynamic methods, the most recent common ancestor of Linyi isolates in sublineage 1a dated back to 24 December 2010, revealing that this sublineage was likely imported into Linyi from August to December in 2010. This study demonstrates that environmental surveillance is a sensitive method in tracing transmission pathways of circulating enteroviruses among different regions and reveals that E6-associated aseptic meningitis is an emerging concern in China.

Evaluating the prevalence and molecular epidemiology of echovirus 11 isolated from sewage in Shandong Province, China in 2010.

Echovirus 11 (E11) is an important human pathogen, but its genetic information in China is in scarce. In this study, 12 sewage samples from Jinan city and 18 from Linyi city were collected in Shandong Province, China in 2010, and E11 was the predominant serotype with 54 isolates from 16 samples. Numbers of E11 isolates reached peaks in August in both Jinan and Linyi city, while another peak occurred in December in Linyi. The complete VP1 genes of all these isolates were sequenced and phylogenetically compared with clinical isolates from Shandong in 1994-2010 (n = 29) and global E11. Shandong isolates segregated into five clusters, four in genogroup A and one in genogroup C. Environmental isolates belonged to two clusters of genogroup A, with high inter-cluster genetic divergence (18.5-20.9%). No local clinical E11 was isolated in the two cities in 2010, revealing the value of environmental surveillance in investigating circulating viruses. These findings underscored the significance of environmental VP1 sequence divergences in comprehending the local enterovirus circulation, and updated the global molecular epidemiology of E11.

Genomic Investigation Reveals a Community Typhoid Outbreak Caused by Contaminated Drinking Water in China, 2016.

Typhoid fever is a life-threatening disease caused by Salmonella enterica serovar Typhi (S. Typhi) and remains a significant public health burden in developing countries. In China, typhoid fever is endemic with a limited number of reported outbreaks. Recently, Chinese local Center for Disease Prevention and Control is starting to apply whole genome sequencing for tracking the source of outbreak isolates. In this study, we conducted a retrospective investigation into a community outbreak of typhoid fever in Lanling, China, in 2016. A total of 26 S. Typhi isolates were recovered from the drinking water (n = 1) and patients' blood (n = 24) and stool (n = 1). Phylogenetic analysis indicated the persistence of the outbreak isolates in drinking water for more than 3 months. The genomic comparison demonstrated a high similarity between the isolate from water and isolates from patients in their genomic content, virulence gene profiles, and antimicrobial resistance gene profile, indicating the S. Typhi isolate from drinking water was responsible for the examined outbreak. The result of pulsed-field gel electrophoresis (PFGE) revealed these isolates had identical PFGE pattern, indicating they are clonal variants. Additionally, phylogeographical analysis of global S. Typhi isolates suggested the outbreak isolates are evolutionarily linked to the isolates from the United Kingdom and Vietnam. Taken together, this study highlights the drinking water and international travel as critical control points of mitigating the outbreak, emphasizing the necessity of regular monitoring of this pathogen in China.

Scalable and accessible personalized photodynamic therapy optimization with FullMonte and PDT-SPACE.

SIGNIFICANCE: Open-source software packages have been extensively used in the past three decades in medical imaging and diagnostics, aiming to study the feasibility of the application ex vivo. Unfortunately, most of the existing open-source tools require some software engineering background to install the prerequisite libraries, choose a suitable computational platform, and combine several software tools to address different applications. AIM: To facilitate the use of open-source software in medical applications, enabling computational studies of treatment outcomes prior to the complex in-vivo setting. APPROACH: FullMonteWeb, an open-source, user-friendly web-based software with a graphical user interface for interstitial photodynamic therapy (iPDT) modeling, visualization, and optimization, is introduced. The software can perform Monte Carlo simulations of light propagation in biological tissues, along with iPDT plan optimization. FullMonteWeb installs and runs the required software and libraries on Amazon Web Services (AWS), allowing scalable computing without complex set up. RESULTS: FullMonteWeb allows simulation of large and small problems on the most appropriate compute hardware, enabling cost improvements of 10 × versus always running on a single platform. Case studies in optical property estimation and diffuser placement optimization highlight FullMonteWeb's versatility. CONCLUSION: The FullMonte open source suite enables easier and more cost-effective in-silico studies for iPDT.

Corrigendum: Genomic Investigation Reveals a Community Typhoid Outbreak Caused by Contaminated Drinking Water in China, 2016.

[This corrects the article DOI: 10.3389/fmed.2022.753085.].

Guanylated Hyperbranched Polylysines with High In Vitro and In Vivo Antifungal Activity.

With the rapid growth of fungal infections and the emergence of multi-drug resistant (MDR) fungal strains, new antifungals with novel mechanisms are a pressing need to tackle this emerging health problem. Herein it is reported for the first time that hyperbranched polylysine (HPL) shows antifungal activities against Candida, especially for drug-sensitive and MDR C. albicans strains, and broad-spectrum antibacterial activities against both Gram-negative and Gram-positive bacteria. The high antimicrobial activities are ascribed to the high charge density and compact size of the globular structure of HPL. The in vitro antifungal activities of HPL3 are further enhanced by the modification of amine groups to form guanylated polylysines (HPL3-Gxs). Similar to antimicrobial peptides (AMPs), HPLs and HPL3-Gxs interact with and lyse the membranes of microbes, which mitigates the emergence of drug resistance. HPLs and HPL3-Gxs demonstrate excellent in vivo antimicrobial efficacies against both lethal C. albicans challenge in the invasive candidiasis model and lethal Methicillin resistant Staphylococcus aureus challenge in the peritonitis model, and have potentials as broad-spectrum antimicrobials.

Metal nanodot memory by self-assembled block copolymer lift-off.

As information technology demands for larger capability in data storage continue, ultrahigh bit density memory devices have been extensively investigated. To produce an ultrahigh bit density memory device, multilevel cell operations that require several states in one cell have been proposed as one solution, which can also alleviate the scaling issues in the current state-of-the-art complementary metal oxide semiconductor technology. Here, we report the first demonstration of metal nanodot memory using a self-assembled block copolymer lift-off. This metal nanodot memory with simple low temperature processes produced an ultrawide memory window of 15 V at the +/-18 V voltage sweep. Such a large window can be adopted for multilevel cell operations. Scanning electron microscopy and transmission electron microscopy studies showed a periodic metal nanodot array with uniform distribution defined by the block copolymer pattern. Consequently, this metal nanodot memory has high potential to reduce the variability issues that metal nanocrystal memories previously had and multilevel cells with ultrawide memory windows can be fabricated with high reliability and manufacturability.

Preparation and characteristic analysis of nanofacula array.

The development of nanofacula array is an effective methods to improve the performance of Near-field Scanning Optical Microscopy (NSOM) and achieve high-throughput array scanning. The nanofacula array is realized by preparing metal nanopore array through the "two etching-one development" method of double-layer resists and the negative lift-off process after metal film coating. The shading property of metal film plays important rules in nanofacula array fabrication. We investigate the shading coefficient of three kinds of metal films (gold-palladium alloy (Au/Pd), platinum (Pt), chromium (Cr)) under different coating times, and 3.5 min Au/Pd film is determined as the candidate of the nanofacula array fabrication for its lower thickness (about 23 nm) and higher shading coefficient (≥ 90%). The nanofacula array is obtained by irradiating with white light (central wavelength of 500 nm) through the metal nanopore array (250/450 nm pore diameter, 2 µm pore spacing and 7 µm group spacing). Moreover, the finite difference and time domain (FDTD) simulation proves that the combination of nanopore array and microlens array achieves high-energy focused nanofacula array, which shows a 3.2 times enhancement of electric field. It provides a new idea for NSOM to realize fast super-resolution focusing facula array.

Eosinophil: A Nonnegligible Predictor in COVID-19 Re-Positive Patients.

Although vaccine resources are being distributed worldwide, insufficient vaccine production remains a major obstacle to herd immunity. In such an environment, the cases of re-positive occurred frequently, and there is a big controversy regarding the cause of re-positive episodes and the infectivity of re-positive cases. In this case-control study, we tracked 39 patients diagnosed with COVID-19 from the Jiaodong Peninsula area of China, of which 7 patients tested re-positive. We compared the sex distribution, age, comorbidities, and clinical laboratory results between normal patients and re-positive patients, and analysed the correlation between the significantly different indicators and the re-positive. Re-positive patients displayed a lower level of serum creatinine (63.38 ± 4.94 U/L vs. 86.82 ± 16.98 U/L; P =0.014) and lower albumin (34.70 ± 5.46 g/L vs. 41.24 ± 5.44 g/L, P =0.039) at the time of initial diagnosis. In addition, two positive phases and the middle negative phase in re-positive patients with significantly different eosinophil counts (0.005 ± 0.005 × 109/L; 0.103 ± 0.033 × 109/L; 0.007 ± 0.115 × 109/L; Normal range: 0.02-0.52 × 109/L). The level of eosinophils in peripheral blood can be used as a marker to predict re-positive in patients who once had COVID-19.