A combined adjuvant approach primes robust germinal center responses and humoral immunity in non-human primates.

Adjuvants and antigen delivery kinetics can profoundly influence B cell responses and should be critically considered in rational vaccine design, particularly for difficult neutralizing antibody targets such as human immunodeficiency virus (HIV). Antigen kinetics can change depending on the delivery method. To promote extended immunogen bioavailability and to present antigen in a multivalent form, native-HIV Env trimers are modified with short phosphoserine peptide linkers that promote tight binding to aluminum hydroxide (pSer:alum). Here we explore the use of a combined adjuvant approach that incorporates pSer:alum-mediated antigen delivery with potent adjuvants (SMNP, 3M-052) in an extensive head-to-head comparison study with conventional alum to assess germinal center (GC) and humoral immune responses. Priming with pSer:alum plus SMNP induces additive effects that enhance the magnitude and persistence of GCs, which correlate with better GC-TFH cell help. Autologous HIV-neutralizing antibody titers are improved in SMNP-immunized animals after two immunizations. Over 9 months after priming immunization of pSer:alum with either SMNP or 3M-052, robust Env-specific bone marrow plasma cells (BM BPC) are observed. Furthermore, pSer-modification of Env trimer reduce targeting towards immunodominant non-neutralizing epitopes. The study shows that a combined adjuvant approach can augment humoral immunity by modulating immunodominance and shows promise for clinical translation.

Antigen pressure from two founder viruses induces multiple insertions at a single antibody position to generate broadly neutralizing HIV antibodies.

Vaccination strategies aimed at maturing broadly neutralizing antibodies (bnAbs) from naïve precursors are hindered by unusual features that characterize these Abs, including insertions and deletions (indels). Longitudinal studies of natural HIV infection cases shed light on the complex processes underlying bnAb development and have suggested a role for superinfection as a potential enhancer of neutralization breadth. Here we describe the development of a potent bnAb lineage that was elicited by two founder viruses to inform vaccine design. The V3-glycan targeting bnAb lineage (PC39-1) was isolated from subtype C-infected IAVI Protocol C elite neutralizer, donor PC39, and is defined by the presence of multiple independent insertions in CDRH1 that range from 1-11 amino acids in length. Memory B cell members of this lineage are predominantly atypical in phenotype yet also span the class-switched and antibody-secreting cell compartments. Development of neutralization breadth occurred concomitantly with extensive recombination between founder viruses before each virus separated into two distinct population "arms" that evolved independently to escape the PC39-1 lineage. Ab crystal structures show an extended CDRH1 that can help stabilize the CDRH3. Overall, these findings suggest that early exposure of the humoral system to multiple related Env molecules could promote the induction of bnAbs by focusing Ab responses to conserved epitopes.

Hydrogel Arrays Enable Increased Throughput for Screening Effects of Matrix Components and Therapeutics in 3D Tumor Models.

Cell-matrix interactions mediate complex physiological processes through biochemical, mechanical, and geometrical cues, influencing pathological changes and therapeutic responses. Accounting for matrix effects earlier in the drug development pipeline is expected to increase the likelihood of clinical success of novel therapeutics. Biomaterial-based strategies recapitulating specific tissue microenvironments in 3D cell culture exist but integrating these with the 2D culture methods primarily used for drug screening has been challenging. Thus, the protocol presented here details the development of methods for 3D culture within miniaturized biomaterial matrices in a multi-well plate format to facilitate integration with existing drug screening pipelines and conventional assays for cell viability. Since the matrix features critical for preserving clinically relevant phenotypes in cultured cells are expected to be highly tissue- and disease-specific, combinatorial screening of matrix parameters will be necessary to identify appropriate conditions for specific applications. The methods described here use a miniaturized culture format to assess cancer cell responses to orthogonal variation of matrix mechanics and ligand presentation. Specifically, this study demonstrates the use of this platform to investigate the effects of matrix parameters on the responses of patient-derived glioblastoma (GBM) cells to chemotherapy.

Electronic Textiles for Wearable Point-of-Care Systems.

Traditional public health systems are suffering from limited, delayed, and inefficient medical services, especially when confronted with the pandemic and the aging population. Fusing traditional textiles with diagnostic, therapeutic, and protective medical devices can unlock electronic textiles (e-textiles) as point-of-care platform technologies on the human body, continuously monitoring vital signs and implementing round-the-clock treatment protocols in close proximity to the patient. This review comprehensively summarizes the research advances on e-textiles for wearable point-of-care systems. We start with a brief introduction to emphasize the significance of e-textiles in the current healthcare system. Then, we describe textile sensors for diagnosis, textile therapeutic devices for medical treatment, and textile protective devices for prevention, by highlighting their working mechanisms, representative materials, and clinical application scenarios. Afterward, we detail e-textiles' connection technologies as the gateway for real-time data transmission and processing in the context of 5G technologies and Internet of Things. Finally, we provide new insights into the remaining challenges and future directions in the field of e-textiles. Fueled by advances in chemistry and materials science, textile-based diagnostic devices, therapeutic devices, protective medical devices, and communication units are expected to interact synergistically to construct intelligent, wearable point-of-care textile platforms, ultimately illuminating the future of healthcare system in the Internet of Things era.

Smart textiles for personalized thermoregulation.

Thermoregulation has substantial implications for human health. Traditional central space heating and cooling systems are less efficient due to wasted energy spent on the entire building and ignore individual thermophysiological comfort. Emerging textiles based on innovations in materials chemistry and physics, nanoscience, and nanotechnology have now facilitated thermoregulation in a far more personalized and energy-saving manner. In this tutorial review, we discuss the latest technological advances in thermoregulatory textiles. First, we outline the basic mechanisms behind the physiological chemistry processes for both internal and external thermoregulation in the human body. Then, we systematically elaborate on typical smart passive and active thermoregulatory textiles considering current working mechanisms, materials engineering towards practical applications. In light of burgeoning commercial trends, we offer important insights into green chemistry for the sustainable development of smart thermoregulatory textiles. Prospectively, we propose an autonomous textile thermoregulation system that could intelligently provide personalized thermophysiological comfort in a self-adaptive manner in the era of Internet of Things (IoT). The discussion of interdisciplinary interactions of energy, environmental science, and nanotechnology in this review will further promote development of the thermoregulatory textile field in both academia and industry, ultimately realizing personalized thermoregulation and a sustainable energy future.

Carbon Nanotube Reinforced Strong Carbon Matrix Composites.

As an excellent candidate for lightweight structural materials and nonmetal electrical conductors, carbon nanotube reinforced carbon matrix (CNT/C) composites have potential use in technologies employed in aerospace, military, and defense endeavors, where the combinations of light weight, high strength, and excellent conductivity are required. Both polymer infiltration pyrolysis (PIP) and chemical vapor infiltration (CVI) methods have been widely studied for CNT/C composite fabrications with diverse focuses and various modifications. Progress has been reported to optimize the performance of CNT/C composites from broad aspects, including matrix densification, CNT alignment, microstructure control, and interface engineering, etc. Recent approaches, such as using resistance heating for PIP or CVI, contribute to the development of CNT/C composites. To deliver a timely and up-to-date overview of CNT/C composites, we have reviewed the most recent trends in fabrication processes, summarized the mechanical reinforcement mechanism, and discussed the electrical and thermal properties, as well as relevant case studies for high-temperature applications. Conclusions and perspectives addressing future routes for performance optimization are also presented. Hence, this review serves as a rundown of recent advances in CNT/C composites and will be a valuable resource to aid future developments in this field.

Smart Textiles for Electricity Generation.

Textiles have been concomitant of human civilization for thousands of years. With the advances in chemistry and materials, integrating textiles with energy harvesters will provide a sustainable, environmentally friendly, pervasive, and wearable energy solution for distributed on-body electronics in the era of Internet of Things. This article comprehensively and thoughtfully reviews research activities regarding the utilization of smart textiles for harvesting energy from renewable energy sources on the human body and its surroundings. Specifically, we start with a brief introduction to contextualize the significance of smart textiles in light of the emerging energy crisis, environmental pollution, and public health. Next, we systematically review smart textiles according to their abilities to harvest biomechanical energy, body heat energy, biochemical energy, solar energy as well as hybrid forms of energy. Finally, we provide a critical analysis of smart textiles and insights into remaining challenges and future directions. With worldwide efforts, innovations in chemistry and materials elaborated in this review will push forward the frontiers of smart textiles, which will soon revolutionize our lives in the era of Internet of Things.

Highly fluorescent copper nanoclusters for sensing and bioimaging.

Metal nanoclusters (NCs), typically consisting of a few to tens of metal atoms, bridge the gap between organometallic compounds and crystalline metal nanoparticles. As their size approaches the Fermi wavelength of electrons, metal NCs exhibit discrete energy levels, which in turn result in the emergence of intriguing physical and chemical (or physicochemical) properties, especially strong fluorescence. Compared with noble metals, copper is a relatively earth-abundant and cost-effective metal. Theoretical and experimental studies have shown that copper NCs (CuNCs) possess unique photoluminescent properties. To highlight these achievements, this review begins by providing an overview of a multitude of factors that play central roles in the fluorescence of CuNCs. Additionally, a critical perspective of how the aggregation of CuNCs can efficiently improve the florescent stability, tunability and intensity is also discussed. Following, we present representative applications of CuNCs in detection and in-vivo/in-vitro imaging and point out that in-situ generation of CuNCs for sensing and bioimaging may be an entry point for the in-depth studies of CuNCs as an intriguing probe. Finally, we outline current challenges and our perspective on the development of CuNCs.