pH-Responsive Amphiphilic Triblock Fluoropolymers as Assemble Oxygen Nanoshuttles for Enhancing PDT against Hypoxic Tumor.

Photodynamic therapy (PDT) is a cancer treatment strategy that utilizes photosensitizers to convert oxygen within tumors into reactive singlet oxygen (1O2) to lyse tumor cells. Nevertheless, pre-existing tumor hypoxia and oxygen consumption during PDT can lead to an insufficient oxygen supply, potentially reducing the photodynamic efficacy. In response to this issue, we have devised a pH-responsive amphiphilic triblock fluorinated polymer (PDP) using copper-mediated RDRP. This polymer, composed of poly(ethylene glycol) methyl ether acrylate, 2-(diethylamino)ethyl methacrylate, and (perfluorooctyl)ethyl acrylate, self-assembles in an aqueous environment. Oxygen, chlorine e6 (Ce6), and doxorubicin (DOX) can be codelivered efficiently by PDP. The incorporation of perfluorocarbon into the formulation enhances the oxygen-carrying capacity of PDP, consequently extending the lifetime of 1O2. This increased lifetime, in turn, amplifies the PDT effect and escalates the cellular cytotoxicity. Compared with PDT alone, PDP@Ce6-DOX-O2 NPs demonstrated significant inhibition of tumor growth. This study proposes a novel strategy for enhancing the efficacy of PDT.

Targeting and Microenvironment-Activated Nanoreactor for Diabetic Chronic Wound Healing via Multienzyme Cascade Reactions.

The development of cell-like nanoreactors with the ability to initiate biocatalytic cascades under special conditions holds tremendous potential for therapeutic applications. Herein, conformationally gated nanoreactors that respond to the acidic microenvironment of infected diabetic wounds were developed by cucur[8]bituril (CB[8])-based supramolecular assembly. The bioinspired nanoreactors exhibit not only self-regulated permeability and selectivity to control internal enzyme activities by substance exchange but also distinct binding specificities toward Gram-positive and Gram-negative bacteria via noncovalent modification with different ligands. The encapsulation of glucose oxidase (GOx), Fe3O4 nanozyme, and l-arginine (l-Arg) into the nanocarriers enables intelligent activation of multienzyme cascade reactions upon glucose (Glu) uptake to produce gluconic acid (GA) and hydrogen peroxide (H2O2), which is further converted into highly toxic hydroxyl radicals (·OH) for selective antibacterial activity. Moreover, acidic H2O2 promotes the oxidization of l-Arg, leading to the release of nitric oxide (NO). Consequently, this nanoreactor provides a multifunctional and synergistic platform for diabetic chronic wound healing by combining enzyme dynamic therapy with NO gas therapy to combat bacterial infections and inflammation under high blood Glu levels.

Event-based surveillance: Providing early warning for communicable disease threats.

The coronavirus disease 2019 pandemic served as a compelling modern-day reminder of the value of early warning against communicable disease threats in public health. As countries exit the acute phase of the pandemic, there remains a continued need to be vigilant for potential communicable disease threats, particularly as the risk of animal-to-human spillover events is increasing due to climate and land use change. Early warning of emerging threats facilitates earlier public health response, which affords more time to implement public health measures that can help minimize the impact of a particular health threat and protect the health and well-being of the population. One approach to providing early warning for communicable disease and other threats is through event-based surveillance (EBS). However, EBS is not often discussed in the context of public health surveillance. This overview introduces EBS and how it might contribute to providing early warning for communicable disease threats.

Multifunctional protein-based self-assembled nanoplatform: overcoming hypoxic tumor microenvironment for enhanced imaging-guided photodynamic therapy.

Photodynamic therapy (PDT) has emerged as a promising modality for cancer treatment, but its efficacy is often limited by tumour hypoxia. Here, we report the development of a novel protein-based, self-assembled nanoplatform, CAT-I-BODIPY NPs (CIB NPs), to address this limitation. We first design and synthesize an I-BODIPY photosensitizer based on the heavy atom effect and modification of the electron-donating group, which exhibits excellent capabilities in generating reactive oxygen species and enabling near-infrared (NIR) fluorescence imaging. The incorporation of an oxygen-producing enzyme, catalase (CAT), within these nanoassemblies enables in situ oxygen generation to counteract hypoxic constraints. Controllable self-assembly by multiple supramolecular interactions into highly ordered architecture not only guarantees CAT's catalytic activity but also leads to excellent NIR fluorescence imaging ability and enhanced PDT efficacy. Notably, the visualization of optimal accumulation of CIB NPs within tumour sites 18 h post-injection offers precise PDT application guidance. Both in vitro and in vivo studies corroborate the remarkable anti-tumour efficacy of CIB NPs under NIR illumination, providing a significant advancement in PDT. The favourable biosafety profile of CIB NPs further emphasizes their potential for clinical application in hypoxic tumour therapy.

Intraseasonal waning immunity of seasonal influenza vaccine - A systematic review and meta-analysis.

BACKGROUND: Recently, studies have suggested that influenza antibody titers decline with time since vaccination. Duration of vaccine protection is an important factor to determine the optimal timing of vaccination. OBJECTIVE: We aimed to systematically evaluate the implication of waning immunity on the duration of seasonal influenza vaccine antibody response. METHOD: Electronic databases and clinical trial registries were systematically searched to identify phase III/IV randomized clinical trials evaluating the immunogenicity of seasonal influenza vaccines measured by hemagglutination inhibition assay in healthy individuals six months of age and older. Meta-analyses were conducted to compare adjuvanted and standard influenza vaccine responses with time since vaccination. RESULTS: 1918 articles were identified, of which ten were included in qualitative synthesis and seven in quantitative analysis (children; n=3, older adults; n=4). All studies were deemed to be at low risk of bias, except one study deemed at high risk of bias due to missing outcome data. The majority of included studies found a rise in antibody titers at one-month followed by a decline at six-month post-vaccination. At six-months post-vaccination overall risk differences in seroprotection were significantly higher for children vaccinated with adjuvanted compared to standard vaccines (0.29; 95 % confidence interval (CI), 0.14-0.44). A small increase in seroprotection levels was observed among older adults vaccinated with an adjuvanted compared to standard vaccines, which remained constant over six-months (pre-vaccination: 0.03; 95 % CI, 0.00-0.09 and one- and six-months post-vaccination: 0.05; 95 % CI, 0.01-0.09). CONCLUSIONS: Our results found evidence of persistent antibody responses following influenza vaccination over the course of a typical influenza season. Even if influenza vaccine responses wane over a six-month period, vaccination likely still provides a significant advantage in protection, which may be enhanced with adjuvanted vaccines, particularly in children. Further research is needed to identify the exact timing when the decline in antibody response begins to better inform the optimal timing of influenza vaccination programs. TRIAL REGISTRATION: PROSPERO (CRD42019138585).

Controllable Regulation of Ag2 S Quantum-Dot-Mediated Protein Nanoassemblies for Imaging-Guided Synergistic PDT/PTT/Chemotherapy against Hypoxic Tumor.

The combination of phototherapy and chemotherapy holds great potential for cancer treatment, while hypoxia in tumor as well as unexpected drug release largely restricts anticancer therapy. Inspired by the natural intelligence, herein, for the first time, a "bottom-up" protein self-assembly strategy mediated by near-infrared (NIR) quantum dots (QDs) with multicharged electrostatic interactions is presented to develop a tumor microenvironment (TME)-responsive theranostic nanoplatform for imaging-guided synergistic photodynamic therapy (PDT)/photothermal therapy (PTT)/chemotherapy. Catalase (CAT) possesses diverse surface charge distribution under different pH conditions. After modification by chlorin e6 (Ce6), the formulated CAT-Ce6 with patchy negative charges can be assembled with NIR Ag2 S QDs by regulating their electrostatic interactions, allowing for effective incorporation of specific anticancer drug oxaliplatin (Oxa). Such Ag2 S@CAT-Ce6@Oxa nanosystems are able to visualize nanoparticle (NP) accumulation to guide subsequent phototherapy, together with significant alleviation of tumor hypoxia to further enhance PDT. Moreover, the acidic TME triggers controllable disassembly through weakening the CAT surface charge to disrupt electrostatic interactions, allowing for sustained drug release. Both in vitro and in vivo results demonstrate remarkable inhibition of colorectal tumor growth with a synergistic effect. Overall, this multicharged electrostatic protein self-assembly strategy provides a versatile platform for realizing TME-specific theranostics with high efficiency and safety, promising for clinical translation.

Impact of industry sponsorship on the quality of systematic reviews of vaccines: a cross-sectional analysis of studies published from 2016 to 2019.

BACKGROUND: Systematic reviews (SRs) provide the highest level of evidence and inform evidence-based decision making in health care. Earlier studies found association with industry to be negatively associated with methodological quality of SRs. However, this has not been investigated in SRs on vaccines. METHODS: We performed a systematic literature search using MEDLINE and EMBASE in March 2020. The results were restricted to those published between 2016 and 2019 with no language restrictions. Study characteristics were extracted by one person and checked by an experienced reviewer. The methodological quality of the SRs was assessed with the AMSTAR 2 tool by multiple reviewers after a calibration exercise was performed. A summary score for each SR was calculated. The Mann-Whitney U test and Fisher's exact test were performed to compare both groups. RESULTS: Out of 185 SRs that met all inclusion criteria, 27 SRs were industry funded. Those were matched with 30 non-industry funded SRs resulting in a total sample size of 57. The mean AMSTAR 2 summary score across all SRs was 0.49. Overall, the median AMSTAR 2 summary score was higher for the non-industry funded SRs than for the industry-funded SRs (0.62 vs. 0.36; p < .00001). Lower ratings for industry funded SRs were consistent across all but one AMSTAR 2 item, though significantly lower only for three specific items. CONCLUSION: The methodological quality of SRs in vaccination is comparable to SRs in other fields, while it is still suboptimal. We are not able to provide a satisfactory explanation why industry funded SRs had a lower methodological quality than non-industry funded SRs over recent years. Industry funding is an important indicator of methodological quality for vaccine SRs and should be carefully considered when appraising SR quality.

SERS based Y-shaped aptasensor for early diagnosis of acute kidney injury.

Considering the pivotal role of biomarkers in plasma, the development of biomarker specific sensing platforms is of great significance to achieve accurate diagnosis and monitor the occurrence and progress in acute kidney injury (AKI). In this paper, we develop a promising surface-enhanced Raman scattering-based aptasensor for duplex detection of two protein biomarkers in AKI. Exploiting the base-pairing specificity of nucleic acids to form a Y-shaped self-assembled aptasensor, the MGITC labelled gold nanoparticles will be attached to the surface of magnetic beads. In the presence of specific AKI-related biomarkers, the gold nanoparticles will detach from magnetic beads into the supernatant, thus leading to a SERS signal increase, which can be used for the highly sensitive analysis of target biomarkers. In addition, the limit of detection calculated for each biomarker indicates that the SERS-based aptasensor can well meet the detection requirements in clinical applications. Finally, the generality of this sensor in the early diagnosis of AKI is confirmed by using a rat model and spiked plasma samples. This sensing platform provides a facile and general route for sensitive SERS detection of AKI-related biomarkers, which offers great promising utility for in vitro and accurate practical bioassay in AKI early diagnosis.

"On/Off" Switchable Sequential Light-Harvesting Systems Based on Controllable Protein Nanosheets for Regulation of Photocatalysis.

A controllable protein nanostructures-based "On/Off" switchable artificial light-harvesting system (LHS) with sequential multistep energy transfer and photocatalysis was reported herein for mimicking the natural LHS in both structure and function. Single-layered protein nanosheets were first constructed via a reversible covalent self-assembly strategy using cricoid stable protein one (SP1) as building blocks to realize an ordered arrangement of pigments. Fluorescent chromophores like carbon dots (CDs) can be precisely distributed on the protein nanosheets superficially via electrostatic interactions and make the ratio between donors and acceptors adjustable. After being anchored with a photocatalysis center (eosin-5-isothiocyanate, EY), the constructed LHS could sequentially transfer energy between two kinds of chromophores (CD1 and CD2), and further transfer to EY center with a high efficiency of 84%. Interestingly, the Förster resonance energy transfer (FRET) process of our LHS could be reversibly "On/Off" switched by the redox regulated assembly and disassembly of SP1 building blocks. Moreover, the LHS has been further proved to promote the yield of a model cross-coupling hydrogen evolution reaction and regulate the process of the reaction with the FRET process "On/Off" state.

Ranking the relative importance of COVID-19 vaccination strategies in Canada: a priority-setting exercise.

BACKGROUND: When vaccine supplies are anticipated to be limited, necessitating the vaccination of certain groups earlier than others, the assessment of values and preferences of stakeholders is an important component of an ethically sound vaccine prioritization framework. The objective of this study was to conduct a priority-setting exercise to establish an expert stakeholder perspective on the relative importance of COVID-19 vaccination strategies in Canada. METHODS: The priority-setting exercise included a survey of stakeholders that was conducted from July 22 to Aug. 14, 2020. Stakeholders included clinical and public health expert groups, provincial and territorial committees and national Indigenous groups, patient and community advocacy representatives and experts, health professional associations and federal government departments. Survey results were analyzed to identify trends. RESULTS: Of 155 stakeholders contacted, 76 surveys were received for a participation rate of 49%. During a period of anticipated initial vaccine scarcity for all pandemic scenarios, stakeholders generally considered the most important vaccination strategy to be protecting those who are most vulnerable to severe illness and death from COVID-19. This was followed in importance by strategies to protect health care capacity, minimize transmission of SARS-CoV-2 and protect critical infrastructure. INTERPRETATION: This priority-setting exercise established that there is general alignment in the values and preferences across stakeholder groups: the most important vaccination strategy at the time of limited initial vaccine availability is to protect those who are most vulnerable. The findings of this priority-setting exercise provided a timely expert perspective to guide early public health planning for COVID-19 vaccines.

Hierarchical protein self-assembly into dynamically controlled 2D nanoarrays via host-guest chemistry.

A dynamically reversible two-dimensional (2D) protein assembly system was designed based on host-guest interactions and was triggered to disassemble via a competition mechanism. The artificially tunable and reversible protein assembly architectures hold great potential for on/off switches in bio-systems.

Demonstrating the capacity of the National Advisory Committee on Immunization for timely responses to post-market vaccine monitoring signals: Canada's experience with the live-attenuated influenza vaccine.

Over the last several years, the recommended use of the live-attenuated influenza vaccine (LAIV) for children has evolved in the United States (US) in response to evidence of a potential decrease in LAIV effectiveness based on post-market monitoring. These issues were not observed in Canada or elsewhere; consequently, recommendations from Canada's National Advisory Committee on Immunization (NACI) and the US Advisory Committee on Immunization Practices (ACIP) on whether to use LAIV differed for two influenza seasons (2016-2017 and 2017-2018). This retrospective describes how NACI arrived at its recommendations in response to post-market signals of reduced LAIV performance from the US in 2013-2014 and again in 2015-2016. NACI's experience with LAIV marks the first time in Canada where a preferential recommendation on the use of an influenza vaccine in a routine immunization program was reversed. This experience highlights the importance of ongoing post-market monitoring of vaccines, international collaboration and careful consideration of local context to inform vaccine recommendations. NACI's capacity for timely responses to post-market vaccine performance signals will facilitate responsiveness to similar post-market monitoring signals from the coronavirus disease 2019 (COVID-19) vaccines.

Navigating inequities: a roadmap out of the pandemic.

The COVID-19 pandemic has exposed social inequities that rival biological inequities in disease exposure and severity. Merely identifying some inequities without understanding all of them can lead to harmful misrepresentations and deepening disparities. Applying an 'equity lens' to bring inequities into focus without a vision to extinguish them is short-sighted. Interventions to address inequities should be as diverse as the pluralistic populations experiencing them. We present the first validated equity framework applied to COVID-19 that sheds light on the full spectrum of health inequities, navigates their sources and intersections, and directs ethically just interventions. The Equity Matrix also provides a comprehensive map to guide surveillance and research in order to unveil epidemiological uncertainties of novel diseases like COVID-19, recognising that inequities may exist where evidence is currently insufficient. Successfully applied to vaccines in recent years, this tool has resulted in the development of clear, timely and transparent guidance with positive stakeholder feedback on its comprehensiveness, relevance and appropriateness. Informed by evidence and experience from other vaccine-preventable diseases, this Equity Matrix could be valuable to countries across the social gradient to slow the spread of SARS-CoV-2 by abating the spread of inequities. In the race to SARS-CoV-2 vaccines, this urgently needed roadmap can effectively and efficiently steer global leadership towards equitable allocation with diverse strategies for diverse inequities. Such a roadmap has been absent from discussions on managing the COVID-19 pandemic, and is critical for our passage out of it.

Microfluidics-Based Sensing of Biospecies.

Over the past decades, microfluidic devices based on many advanced techniques have aroused widespread attention in the fields of chemical, biological, and analytical applications. Integration of microdevices with a variety of chip designs will facilitate promising functionality. Notably, the combination of microfluidics with functional nanomaterials may provide creative ideas to achieve rapid and sensitive detection of various biospecies. In this review, focused on the microfluids and microdevices in terms of their fabrication, integration, and functions, we summarize the up-to-date developments in microfluidics-based analysis of biospecies, where biomarkers, small molecules, cells, and pathogens as representative biospecies have been explored in-depth. The promising applications of microfluidic biosensors including clinical diagnosis, food safety control, and environmental monitoring are also discussed. This review aims to highlight the importance of microfluidics-based biosensors in achieving high throughput, highly sensitive, and low-cost analysis and to promote microfluidics toward a wider range of applications.

Engineering Nonmechanical Protein-Based Hydrogels with Highly Mechanical Properties: Comparison with Natural Muscles.

The elegant elasticity and toughness of muscles that are controlled by myofilament sliding, highly elastic springlike properties of titin, and Ca2+-induced conformational change of the troponin complex have been a source of inspiration to develop advanced materials for simulating elastic muscle motion. Herein, a highly stretchable protein hydrogel is developed to mimic the structure and motion of muscles through the combination of protein folding-unfolding and molecular sliding. It has been shown that the protein bovine serum albumin is covalently cross-linked, together penetrated with alginate chains to construct polyprotein-based hydrogels, where polyproteins can act as the elastic spring titin via protein folding-unfolding and also achieve tunable sliding facilitated by alginate due to their reversible noncovalent interactions, thus providing desired mechanical properties such as stretchability, resilience, and strength. Notably, these biomaterials can achieve the breaking strain of up to 1200% and show massive energy dissipation. A pronounced expansion-contraction phenomenon is also observed on the macroscopic scale, and the Ca2+-induced contraction process may help to improve our understanding of muscle movement. Overall, these excellent properties are comparable to or even better than those of natural muscles, making the polyprotein-based hydrogels represent a new type of muscle-mimetic biomaterial. Significantly, the prominent biocompatibility of the designed biomaterials further enables them to hold potential applications in the biomedical field and tissue engineering.

Visualization of carboxylesterase 2 with a near-infrared two-photon fluorescent probe and potential evaluation of its anticancer drug effects in an orthotopic colon carcinoma mice model.

We establish a near-infrared two-photon fluorescent probe for the detection of CE2 with high selectivity and sensitivity. This probe exhibits low cytotoxicity and superior tissue penetration ability for evaluating the real-time activity of CE2 in living cells, in cancer tissues, and in a colon carcinoma mice model.

Tumor Microenvironment-Specific Functional Nanomaterials for Biomedical Applications.

In recent years, considerable achievements have been made to motivate the construction of tumor microenvironment (TME)-specific functional nanomaterials, which can effectively respond to the inherent pathological and physicochemical conditions in diseased regions to improve the specificity of imaging and drug delivery. Until now, various nanoarchitectures have been designed to combat cancer effectively and specifically. This review summarizes the latest developments in TME-specific theranostic nanoplatforms based on multifunctional nanomaterials that hold potential for achieving the targeted recognition at tumor sites. Recent progress and achievements have also been summarized for nanosystems that can specifically respond to the TME with various stimulus-responsive strategies and their applications for drug delivery, diagnosis, treatment, and synergistic theranostics of cancer. This review emphasizes the significance of functional nanomaterials in response to tumor stimuli to enhance anticancer treatment efficiency and facilitate development in extensive research fields, including nanoscience, biomedicine, and clinical applications.

Self-Assembled Nanomaterials for Enhanced Phototherapy of Cancer.

Following the wisdom of nature to assemble functional candidates into exquisite nanoarchitectures is emerging as a promising field of research and has been widely applied in biomedical sciences. Owing to their excellent properties of structural controllability, functional diversity, dynamic adjustability, and prominent biocompatibility, the self-assembled nanoarchitectures come to play a pivotal role in fighting against cancer. This review outlines the most up-to-date developments in constructing phototherapeutic nanomaterials for photodynamic and photothermal therapy (PDT and PTT) of tumors, with emphasis on design ideas, building blocks, and advantageous characteristics of self-assembly. The prominent activities of cancer therapy obtained by these photoinduced nanotheranostics are also explored in-depth, together with the connections between the specific nanostructures and unique features, providing a comprehensive understanding of the self-assembled nanomaterials in improving the outcomes of PDT and PTT. This review aims to highlight the significance of self-assembled nanomaterials in enhancing phototherapeutic efficacy and to promote its development in various research interests ranging from material science and nanoscience to biomedicine and clinical medicine.