Colloidal quasicrystals engineered with DNA.

In principle, designing and synthesizing almost any class of colloidal crystal is possible. Nonetheless, the deliberate and rational formation of colloidal quasicrystals has been difficult to achieve. Here we describe the assembly of colloidal quasicrystals by exploiting the geometry of nanoscale decahedra and the programmable bonding characteristics of DNA immobilized on their facets. This process is enthalpy-driven, works over a range of particle sizes and DNA lengths, and is made possible by the energetic preference of the system to maximize DNA duplex formation and favour facet alignment, generating local five- and six-coordinated motifs. This class of axial structures is defined by a square-triangle tiling with rhombus defects and successive on-average quasiperiodic layers exhibiting stacking disorder which provides the entropy necessary for thermodynamic stability. Taken together, these results establish an engineering milestone in the deliberate design of programmable matter.

Two phases based training method for designing codewords for a set of perceptrons with each perceptron having multi-pulse type activation function.

This paper proposes a two phases-based training method to design the codewords to map the cluster indices of the input feature vectors to the outputs of the new perceptrons with the multi-pulse type activation functions. Our proposed method is applied to classify two types of the tachycardias. First, the total number of the new perceptrons is initialized as the dimensions of the input feature vectors. Next, a set of new perceptrons with each new perceptron having a single pulse type activation function is designed. Then, the new perceptrons with the multi-pulse type activation function are designed based on those new perceptrons with the single pulse type activation function. After that, the codewords are assigned according to the outputs of the new perceptrons with the multi-pulse type activation functions. Finally, a condition on the codewords is checked. The significance of this work is to guarantee to achieve the no classification error efficiently through using more than one new perceptron with the multi-pulse type activation if the feature space can be linearly partitioned into the multiple clusters. The computer numerical simulation results show that our proposed method outperforms the conventional perceptrons with the sign type activation function.

Tumor cell lysate-loaded immunostimulatory spherical nucleic acids as therapeutics for triple-negative breast cancer.

Highly heterogenous cancers, such as triple-negative breast cancer (TNBC), remain challenging immunotherapeutic targets. Herein, we describe the synthesis and evaluation of immunotherapeutic liposomal spherical nucleic acids (SNAs) for TNBC therapy. The SNAs comprise immunostimulatory oligonucleotides (CpG-1826) as adjuvants and encapsulate lysates derived from TNBC cell lines as antigens. The resulting nanostructures (Lys-SNAs) enhance the codelivery of adjuvant and antigen to immune cells when compared to simple mixtures of lysates with linear oligonucleotides both in vitro and in vivo, and reduce tumor growth relative to simple mixtures of lysate and CpG-1826 (Lys-Mix) in both Py230 and Py8119 orthotopic syngeneic mouse models of TNBC. Furthermore, oxidizing TNBC cells prior to lysis and incorporation into SNAs (OxLys-SNAs) significantly increases the activation of dendritic cells relative to their nonoxidized counterparts. When administered peritumorally in vivo in the EMT6 mouse mammary carcinoma model, OxLys-SNAs significantly increase the population of cytotoxic CD8+ T cells and simultaneously decrease the population of myeloid derived suppressor cells (MDSCs) within the tumor microenvironment, when compared with Lys-SNAs and simple mixtures of oxidized lysates with CpG-1826. Importantly, animals administered OxLys-SNAs exhibit significant antitumor activity and prolonged survival relative to all other treatment groups, and resist tumor rechallenge. Together, these results show that the way lysates are processed and packaged has a profound impact on their immunogenicity and therapeutic efficacy. Moreover, this work points toward the potential of oxidized tumor cell lysate-loaded SNAs as a potent class of immunotherapeutics for cancers lacking common therapeutic targets.

Device-quality, reconfigurable metamaterials from shape-directed nanocrystal assembly.

Anchoring nanoscale building blocks, regardless of their shape, into specific arrangements on surfaces presents a significant challenge for the fabrication of next-generation chip-based nanophotonic devices. Current methods to prepare nanocrystal arrays lack the precision, generalizability, and postsynthetic robustness required for the fabrication of device-quality, nanocrystal-based metamaterials [Q. Y. Lin et al. Nano Lett. 15, 4699-4703 (2015); V. Flauraud et al., Nat. Nanotechnol. 12, 73-80 (2017)]. To address this challenge, we have developed a synthetic strategy to precisely arrange any anisotropic colloidal nanoparticle onto a substrate using a shallow-template-assisted, DNA-mediated assembly approach. We show that anisotropic nanoparticles of virtually any shape can be anchored onto surfaces in any desired arrangement, with precise positional and orientational control. Importantly, the technique allows nanoparticles to be patterned over a large surface area, with interparticle distances as small as 4 nm, providing the opportunity to exploit light-matter interactions in an unprecedented manner. As a proof-of-concept, we have synthesized a nanocrystal-based, dynamically tunable metasurface (an anomalous reflector), demonstrating the potential of this nanoparticle-based metamaterial synthesis platform.

Risk factors associated with the prevalence of neck and shoulder pain among high school students: a cross-sectional survey in China.

BACKGROUND: After the COVID-19 outbreak, many Chinese high school students have increased their dependence on electronic devices for studying and life, which may affect the incidence of neck and shoulder pain (NSP) in Chinese adolescents. METHODS: To evaluate the prevalence of NSP in high school students and its associated risk factors during COVID-19, a survey was conducted among 5,046 high school students in Shanghai, Qinghai, Henan and Macao during the second semester and summer vacation of the 2019-2020 academic year. The questionnaire included questions regarding demographic characteristics, the prevalence of NSP and lifestyle factors such as sedentary behavior, poor posture and electronic device usage. Univariable and multivariable logistic regression was used to analyze the possible influencing factors for neck and shoulder pain. RESULTS: A total of 4793 valid questionnaires (95.0%) were collected. The results indicated that the prevalence of NSP was 23.7% among high school students. Binary logistic regression analysis revealed that female gender (P < 0.05, OR = 1.82), grade (P < 0.05, range OR 1.40-1.51) and subject selection (P < 0.05, range OR 0.49-0.68) were risk factors for NSP in high school students. Sedentary behavior (P < 0.05, range OR 1.74-2.36), poor posture (P < 0.05, range OR 1.19-2.56), backpack weight (P < 0.05, range OR 1.17-1.88), exercise style and frequency (P < 0.05, range OR 1.18-1.31; P < 0.05, range OR 0.76-0.79, respectively), and the time spent using electronic devices (P < 0.05, range OR 1.23-1.38)had a significant correlation with NSP in high school students. CONCLUSIONS: NSP is currently very common among high school students during the outbreak of COVID-19. Sedentary behavior, poor posture and other factors have a great impact on the occurrence of NSP in high school students. Education regarding healthy lifestyle choices should be advocated for to decrease NSP among high school students, such as more physical activity, changing poor postures and reducing the amount of time spent using electronic devices.

Rational vaccinology with spherical nucleic acids.

In the case of cancer immunotherapy, nanostructures are attractive because they can carry all of the necessary components of a vaccine, including both antigen and adjuvant. Herein, we explore how spherical nucleic acids (SNAs), an emerging class of nanotherapeutic materials, can be used to deliver peptide antigens and nucleic acid adjuvants to raise immune responses that kill cancer cells, reduce (or eliminate) tumor growth, and extend life in three established mouse tumor models. Three SNA structures that are compositionally nearly identical but structurally different markedly vary in their abilities to cross-prime antigen-specific CD8+ T cells and raise subsequent antitumor immune responses. Importantly, the most effective structure is the one that exhibits synchronization of maximum antigen presentation and costimulatory marker expression. In the human papillomavirus-associated TC-1 model, vaccination with this structure improved overall survival, induced the complete elimination of tumors from 30% of the mice, and conferred curative protection from tumor rechallenges, consistent with immunological memory not otherwise achievable. The antitumor effect of SNA vaccination is dependent on the method of antigen incorporation within the SNA structure, underscoring the modularity of this class of nanostructures and the potential for the deliberate design of new vaccines, thereby defining a type of rational cancer vaccinology.

Lipid Nanoparticle Spherical Nucleic Acids for Intracellular DNA and RNA Delivery.

Lipid nanoparticle SNAs (LNP-SNAs) have been synthesized for the delivery of DNA and RNA to targets in the cytoplasm of cells. Both the composition of the LNP core and surface-presented DNA sequences contribute to LNP-SNA activity. G-rich sequences enhance the activity of LNP-SNAs compared to T-rich sequences. In the LNP core, increased cholesterol content leads to greater activity. Optimized LNP-SNA candidates reduce the siRNA concentration required to silence mRNA by 2 orders of magnitude compared to liposome-based SNAs. In addition, the LNP-SNA architectures alter biodistribution and efficacy profiles in mice. For example, mRNA within LNP-SNAs injected intravenously is primarily expressed in the spleen, while mRNA encapsulated by LNPs (no DNA on the surface) was expressed primarily in the liver with a relatively small amount in the spleen. These data show that the activity and biodistribution of LNP-SNA architectures are different from those of conventional liposomal SNAs and therefore potentially can be used to target tissues.

Initial Outcomes of Transdiagnostic Internet-Delivered Cognitive Behavioral Therapy Tailored to Public Safety Personnel: Longitudinal Observational Study.

BACKGROUND: Canadian public safety personnel (PSP) experience high rates of mental health disorders and face many barriers to treatment. Internet-delivered cognitive behavioral therapy (ICBT) overcomes many such barriers, and is effective for treating depression, anxiety, and posttraumatic stress disorder (PTSD) symptoms. OBJECTIVE: This study was designed to fill a gap in the literature regarding the use of ICBT tailored specifically for PSP. We examined the effectiveness of a tailored ICBT program for treating depression, anxiety, and PTSD symptoms among PSP in the province of Saskatchewan. METHODS: We employed a longitudinal single-group open-trial design (N=83) with outcome measures administered at screening and at 8 weeks posttreatment. Data were collected between December 5, 2019 and September 11, 2020. Primary outcomes included changes in depression, anxiety, and PTSD symptoms. Secondary outcomes included changes in functional impairment; symptoms of panic, social anxiety, and anger; as well as treatment satisfaction, working alliance, and program usage patterns. RESULTS: Clients reported large symptom reductions on measures of depression and anxiety, as well as moderate reductions on measures of PTSD and secondary symptoms, except for social anxiety. Most clients who reported symptoms above clinical cut-offs on measures of depression, anxiety, and PTSD during screening experienced clinically significant symptom reductions. Results suggested good engagement, treatment satisfaction, and working alliance. CONCLUSIONS: Tailored, transdiagnostic ICBT demonstrated promising outcomes as a treatment for depression, anxiety, and PTSD among Saskatchewan PSP and warrants further investigation. TRIAL REGISTRATION: Clinicaltrials.gov NCT04127032; https://www.clinicaltrials.gov/ct2/show/NCT04127032.

Endosomal Organization of CpG Constructs Correlates with Enhanced Immune Activation.

This Letter describes how the endosomal organization of immunostimulatory nanoconstructs can tune the in vitro activation of macrophages. Nanoconstructs composed of gold nanoparticles conjugated with unmethylated cytosine-phosphate-guanine (CpG) oligonucleotides have distinct endosomal distributions depending on the surface curvature. Mixed-curvature constructs produce a relatively high percentage of hollow endosomes, where constructs accumulated primarily along the interior edges. These constructs achieved a higher level of toll-like receptor (TLR) 9 activation along with the enhanced secretion of proinflammatory cytokines and chemokines compared to constant-curvature constructs that aggregated mostly in the center of the endosomes. Our results underscore the importance of intraendosomal interactions in regulating immune responses and targeted delivery.

Enhanced Photodetection Properties of Tellurium@Selenium Roll-to-Roll Nanotube Heterojunctions.

Non-layered tellurium (Te) is a promising material for applications in transistor and optoelectronic devices for its advantages in excellent intrinsic electronic and optoelectronic properties. However, the poor photodetection performance and relatively uncertain stability of tellurene under ambient conditions greatly limit the practical applications. In order to improve the performance of tellurene-based materials, Te@Se roll-to-roll nanotubes with different selenium (Se) contents synthesized by epitaxial growth of Se on Te nanotubes are, for the first time, employed to fabricate working electrodes for photoelectrochemical (PEC)-type broadband photodetection. They exhibit not only a preferably enhanced capacity for self-powered broadband photodetection but also significantly improved photocurrent density and stability in various aqueous environments (HCl, NaCl, and KOH solutions), compared to tellurene-based photodetectors. It is anticipated that the present work can open up new possibilities for high-performance tellurene-based optoelectronic devices.

Space-tiled colloidal crystals from DNA-forced shape-complementary polyhedra pairing.

Generating space-filling arrangements of most discrete polyhedra nanostructures of the same shape is not possible. However, if the appropriate individual building blocks are selected (e.g., cubes), or multiple shapes of the appropriate dimensions are matched (e.g., octahedra and tetrahedra) and their pairing interactions are subsequently forced, space-filled architectures may be possible. With flexible molecular ligands (polyethylene glycol-modified DNA), the shape of a polyhedral nanoparticle can be deliberately altered and used to realize geometries that favor space tessellation. In this work, 10 new colloidal crystals were synthesized from DNA-modified nanocrystal building blocks that differed in shapes and sizes, designed to form space-filling architectures with micron-scale dimensions. The insights and capabilities provided by this new strategy substantially expand the scope of colloidal crystals possible and provide an expanded tool kit for researchers interested in designing metamaterials.

Association between AGTR1 (c.1166 A>C) Polymorphisms and Kidney Injury in Hypertension.

BACKGROUND: High blood pressure is the main cause of cardiovascular diseases. Kidney damage is one of the most common organ secondary damage to hypertension. The study of hypertension gene polymorphisms is an important means of precision treatment of primary hypertension. OBJECTIVES: The objective of this study was to explore the relationship between AGTR1 (c.1166 A>C) gene polymorphisms and hypertension combined with kidney damage, while exploring the relationship between codominant, dominant and recessive gene model and hypertension with kidney injury and the susceptibility of different genotypes to hypertension with kidney injury. METHODS: The distribution of AGTR1 polymorphism in the AGTR1 in hypertensive patients (hypertension group, 292 patients) and hypertension with kidney injury patients (44 patients) were detected and compared by PCR-melting curve method. RESULTS: The genotype distribution of hypertension and combined groups met Hardy-Weinberg equilibrium (p > 0.05); the distribution difference between the three genotypes was statistically significant (p < 0.05), the codominant, dominant and recessive distribution frequency of genotypes (p < 0.05), and no difference between A allele and C allele (p > 0.05). CONCLUSIONS: Our study identified the relationship of AGTRA (c.1166 A>C) with hypertension combined with renal injury, and compared the susceptibility of different genetic models, which may provide novel targets for precision gene therapy of hypertension. CLINICAL TRIAL REGISTRATION: URL: https://www.chictr.org.cn/indexEN.html; Unique identifier: ChiCTR2100051472.

Functional System Based on Glycyrrhizic Acid Supramolecular Hydrogel: Toward Polymorph Control, Stabilization, and Controlled Release.

Developments of a drug delivery system (DDS) based on a natural supramolecular hydrogel have been of wide interest due to its biocompatibility, efficacy, and adjustable performance. However, a simple and efficient design of functional hydrogel DDS based on the templated interplay of gelator and model drug is still a challenge. In this work, natural glycyrrhetinic acid (GA) gel was selected as a carrier to encapsulate the model drug pyrazinamide (PZA). It was found that the carboxyl-amide interaction at the interface of gel-drug achieved polymorph control, stabilization, and pH-responsive release. Powder X-ray diffraction confirmed that the metastable γ form of PZA was obtained from the GA gel. Spectral analysis and molecular dynamics simulation showed that the protonation at the amide-O promoted the discretization of PZA molecules in solution, resulting in the polymorphism. Furthermore, the gel-drug interplay increased the stability of the γ form significantly from 2 days to 3 months by in situ encapsulation in the GA gel. In vitro release study indicated that the GA gel achieved targeted control release of PZA due to the pH-responsiveness property of GA. This work provides a promising option for hydrogel-based DDS design combined with polymorph control and stabilization.

Efficacy and safety of EUS-guided coil embolization combined with endoscopic cyanoacrylate injection versus balloon-occluded retrograde transvenous obliteration for gastric varices with high-risk ectopic embolism: A multicenter and retrospective cohort study.

Background and Objectives: Gastric varices (GV) with spontaneous portosystemic shunt (SPSS) are associated with ectopic embolism in endoscopic cyanoacrylate. This study targeted to assess the efficacy and safety of EUS-guided coil embolization combined with endoscopic cyanoacrylate injection versus balloon-occluded retrograde transvenous obliteration (BRTO) for GV with high-risk ectopic embolism. Materials and Methods: We retrospectively analyzed six tertiary hospitals' 104 patients with GV at high-risk ectopic embolism (the narrowest diameter of SPSS was greater than or equal to 5 mm and the maximum diameter usually >8 mm) who underwent EUS-guided coil embolization combined with endoscopic cyanoacrylate injection or BRTO from January 2014 to December 2020. The outcomes included rebleeding, survival, and complications. Results: The EUS group and BRTO group contained 59 and 45 patients, respectively. The technical success rate between the two groups was similar (96.6% vs. 95.6%, P = 1.000). During the follow-up, both groups' 5-day rebleeding rate and 6-week mortality rate were 0%. One-year all-cause rebleeding rate (20.0% vs. 18.9%, P = 0.900) and 1-year mortality rate (2.0% vs. 0%, P = 1.000) in the EUS group were similar to the BRTO group. One patient experienced ectopic embolism in the EUS group, while the BRTO group did not. Both groups had similar mean days (16.0 [interquartile range (IQR), 12.0-19.0] vs. 16.5 [IQR, 11.8-26.0], P = 0.165) and cost of hospitalization (¥ 45950.6 [IQR, 39330.2-55768.2] vs. ¥ 51205.8 [IQR, 31628.8-74251.5], P = 0.680). Multivariate analysis showed that the narrowest diameter of the shunt (odds ratio [OR] = 1.86; 95% confidence interval [CI]: 1.062-3.258; P = 0.03) and content of hemoglobin (OR = 0.941; 95% CI: 0.892-0.992; P = 0.025) were the prognostic factors for survival. Conclusions: The efficacy and safety of EUS-guided coil embolization combined with endoscopic cyanoacrylate injection for GV with high-risk ectopic embolism are comparable to BRTO.

Double Gain: The Radio Frequency Catheter Ablation of Ventricular Aneurysm Related Recurrent Ventricular Tachycardia on a Tremendous Cardiac Outpouching.

Dilated cardiomyopathy (DCM) is a classic type of non-ischemic cardiomyopathy. Of these, idiopathic cardiomyopathy (IDCM) is a rare type of non-genetic dilated cardiomyopathy. More specifically, the patient had suspected IDCM combined with sustained polymorphic ventricular tachycardia (PMVT) of left ventricular basal segmental origin, cardiac systolic dysfunction and an ejection fraction (EF) of 29%. He had an abnormally large ventricular aneurysm (VA) in the posterior wall of the left ventricle with left ventricular end diastolic dimension (LVDd) of 90 mm. We performed an endocardial radiofrequency catheter ablation (RFCA) of the patient's recurrent ventricular tachycardia (VT) on the basis of an implantable cardioverter (ICD). Although minimally invasive RFCA also carries a high risk, it is currently a two-pronged option to improve the patient's quality of life and to prevent the recurrence of VT. Postoperatively, the patient was routinely given optimal anti-arrhythmic and heart failure (HF) treatments to improve cardiac function as well as being followed up for 9 months. The patient's EF ascended to 36% without any recurrence of VT. In summary, RFCA of suspected IDCM combined with VA and VT of basal area origin would be an effective treatment.

Rational Vaccinology: Harnessing Nanoscale Chemical Design for Cancer Immunotherapy.

Cancer immunotherapy is a powerful treatment strategy that mobilizes the immune system to fight disease. Cancer vaccination is one form of cancer immunotherapy, where spatiotemporal control of the delivery of tumor-specific antigens, adjuvants, and/or cytokines has been key to successfully activating the immune system. Nanoscale materials that take advantage of chemistry to control the nanoscale structural arrangement, composition, and release of immunostimulatory components have shown significant promise in this regard. In this Outlook, we examine how the nanoscale structure, chemistry, and composition of immunostimulatory compounds can be modulated to maximize immune response and mitigate off-target effects, focusing on spherical nucleic acids as a model system. Furthermore, we emphasize how chemistry and materials science are driving the rational design and development of next-generation cancer vaccines. Finally, we identify gaps in the field that should be addressed moving forward and outline future directions to galvanize researchers from multiple disciplines to help realize the full potential of this form of cancer immunotherapy through chemistry and rational vaccinology.

Heart Failure with Supra-normal Left Ventricular Ejection Fraction - State of the Art. / Insuficiência Cardíaca com Fração de Ejeção Ventricular Esquerda Supranormal - Estado da Arte.

In 2019, an article published in the European Heart Journal recognized for the first time heart failure (HF) with left ventricular ejection fraction (LVEF)≥ 65% as a new HF phenotype, heart failure with supra-normal left ventricular ejection fraction (HFsnEF), with the main purpose of promoting research on this new category. They analyzed mortality in people with HF and found that there was a u-shaped relationship between mortality and LVEF. Accordingly, HFsnEF patients had a higher all-cause mortality compared with other patients diagnosed with HF with preserved ejection fraction (HFpEF). This article describes the current situation of HFsnEF and discusses future perspectives based on the preliminary results of our group. To better treat patients with HFsnEF, it is fundamental that cardiologists and physicians understand the differences and similarities of this new phenotype.

Em 2019, um artigo publicado no European Heart Journal reconheceu pela primeira vez a insuficiência cardíaca (IC) com fração de ejeção do ventrículo esquerdo (FEVE) ≥ 65% como um novo fenótipo de IC, ou a insuficiência cardíaca com fração de ejeção supranormal (ICFEsn), com o objetivo principal de promover a investigação desta nova categoria. Eles analisaram a mortalidade em pessoas com IC e descobriram que havia uma relação em forma de U entre a mortalidade e a FEVE. Sendo assim, os pacientes com ICFEsn tinham uma mortalidade geral mais alta em comparação com outros pacientes diagnosticados com IC com fração de ejeção preservada (ICFEp). Este artigo descreve a situação atual da ICFEsn e discute as perspectivas futuras com base nos resultados preliminares de nosso grupo. Para melhor tratar os pacientes com ICFEsn, é fundamental que cardiologistas e médicos entendam as diferenças e semelhanças desse novo fenótipo.

Gut Microbiota in Heart Failure Patients With Preserved Ejection Fraction (GUMPTION Study).

Introduction: Heart failure with preserved ejection fraction (HFpEF) is associated with disrupted intestinal epithelial function, resulting from intestinal congestion. Intestinal congestion changes the morphology and permeability of the intestinal wall, and it becomes easy for the gut microbiota to change and transfer. Intervention on gut microbiota may become a new target for HFpEF treatment. However, the characteristics of gut microbiota in patients with HFpEF remain unknown. This preliminary report aims to detect the structure of gut microbiota in HFpEF patients so as to explore their characteristic changes, thereby providing a theoretical basis for future research. Methods: This research recruited 30 patients diagnosed with HFpEF and 30 healthy individuals. Stool specimens of research subjects were collected separately, and the microarray analyses of gut microbiota were conducted by Illumina high-throughput DNA sequencing. The differences in gut microbiota composition, alpha diversity, and beta diversity between the two groups were finally obtained. Results: The composition of gut microbiota was significantly different between the two groups. At the phylum classification level, the abundance of Synergistetes tended to be higher in the HFpEF group (P = 0.012). At genus classification level, the abundance of Butyricicoccus (P < 0.001), Sutterella (P = 0.004), Lachnospira (P = 0.003), and Ruminiclostridium (P = 0.009) in the HFpEF group were lower, while the abundance of Enterococcus (P < 0.001) and Lactobacillus (P = 0.005) were higher. According to the Chao index of alpha diversity analysis, HFpEF patients showed a nominally significant lower species richness when compared with controls (P = 0.046). However, there was no statistical difference in the Shannon index (P = 0.159) and Simpson index (P = 0.495), indicating that there was no difference in species diversity between the two groups. Beta diversity analysis revealed a highly significant separation of HFpEF patients and controls. Conclusions: An imbalance in the gut microbiota of HFpEF patients was observed. Patients with HFpEF have an increased abundance of microbiota associated with inflammation and a decreased abundance of microbiota associated with anti-inflammatory effects in the gut environment. In line with that, the species richness of gut microbiota in HFpEF patients tended to be lower.

Synergistic Immunostimulation through the Dual Activation of Toll-like Receptor 3/9 with Spherical Nucleic Acids.

Toll-like receptors (TLRs) are a family of proteins that modulate the innate immune system and control the initiation of downstream immune responses. Spherical nucleic acids (SNAs) designed to stimulate single members of the TLR family (e.g., TLR7 or TLR9) have shown utility in cancer immunotherapy. We hypothesized that SNAs synthesized with multiple TLR agonists would enable the simultaneous activation of multiple TLR pathways for maximally synergistic immune activation. Here, we describe the synthesis of SNAs that incorporate both a TLR3 agonist (polyinosinic:polycytidylic acid, poly(I:C)) and TLR9 agonist (CpG oligonucleotide) on the same liposomal scaffold. In this design, CpG comprises the SNA oligonucleotide shell, and poly(I:C) is encapsulated in the liposome core. These dual-TLR activating SNAs efficiently codeliver high quantities of both agonists to the same target cell, yielding enhanced immunostimulation in various murine and human antigen-presenting cells (APCs). Moreover, codelivery of TLR agonists using the SNA both synchronizes and prolongs the duration of costimulatory molecule and major histocompatibility complex class II expression in APCs, which has been shown to be important for efficient downstream immune responses. Taken together, this SNA design provides a strategy for potently activating immune cells and increasing the efficiency of their activation, which likely will inform the preparation of nanomaterials for highly potent immunotherapies.

Inhibitors of the renin-angiotensin system: The potential role in the pathogenesis of COVID-19.

Coronavirus disease 2019 (COVID-19), which initially began in China, has spread to other countries of Asia, Europe, America, Africa and Oceania, with the number of confirmed cases and suspected cases increasing each day. According to recently published research, it was found that the majority of the severe cases were elderly, and many of them had at least one chronic disease, especially cardiovascular diseases. Angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEIs/ARBs) are the most widely used drugs for cardiovascular diseases. The clinical effect of ACEIs/ARBs on patients with COVID-19 is still uncertain. This paper describes their potential role in the pathogenesis of COVID-19, which may provide useful in the advice of cardiologists and physicians.