Construction of Fosmid-based SARS-CoV-2 replicons for antiviral drug screening and replication analyses in biosafety level 2 facilities.

The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has necessitated the global development of countermeasures since its outbreak. However, current therapeutics and vaccines to stop the pandemic are insufficient and this is mainly because of the emergence of resistant variants, which requires the urgent development of new countermeasures, such as antiviral drugs. Replicons, self-replicating RNAs that do not produce virions, are a promising system for this purpose because they safely recreate viral replication, enabling antiviral screening in biosafety level (BSL)-2 facilities. We herein constructed three pCC2Fos-based RNA replicons lacking some open reading frames (ORF) of SARS-CoV-2: the Δorf2-8, Δorf2.4, and Δorf2 replicons, and validated their replication in Huh-7 cells. The functionalities of the Δorf2-8 and Δorf2.4 replicons for antiviral drug screening were also confirmed. We conducted puromycin selection following the construction of the Δorf2.4-puro replicon by inserting a puromycin-resistant gene into the Δorf2.4 replicon. We observed the more sustained replication of the Δorf2.4-puro replicon by puromycin pressure. The present results will contribute to the establishment of a safe and useful replicon system for analyzing SARS-CoV-2 replication mechanisms as well as the development of novel antiviral drugs in BSL-2 facilities.

Synthesis, applications and biosafety evaluation of carbon dots derived from herbal medicine.

Carbon dots (CDs) are novel zero-dimensional spherical nanoparticles with water solubility, biocompatibility and photoluminescence properties. As the variety of raw materials for CDs synthesis becomes more and more abundant, people tend to choose precursors from nature. Many recent studies have shown that CDs can inherit properties similar to their carbon sources. Chinese herbal medicine has a variety of therapeutic effects to many diseases. In recent years, many literatures have chosen herbal medicine as raw materials, however, how the properties of raw materials affect CDs has not been systematically summarized. The intrinsic bioactivity and potential pharmacological effects of CDs have not received sufficient attention and have become a 'blind spot' for research. In this paper, the main synthesis methods were introduced and the effects of carbon sources from different herbal medicine on the properties of CDs and related applications were reviewed. In addition, we briefly review some of the biosafety assessments of CDs, and make recommendations for biomedical applications. CDs that inherit the therapeutic properties of herbs can enable diagnosis and treatment of clinical diseases, bioimaging, and biosensing in the future.

Self-assembled nano-photosensitizer for targeted, activatable, and biosafe cancer phototheranostics.

Cancer treatment currently still faces crucial challenges in therapeutic effectiveness, precision, and complexity. Photodynamic therapy (PDT) as a non-invasive tactic has earned widespread popularity for its excellent therapeutic output, flexibility, and restrained toxicity. Nonetheless, drawbacks, including low efficiency, poor cancer specificity, and limited therapeutic depth, remain considerable during the cancer treatment. Although great effort has been made to improve the performance, the overall efficiency and biosafety are still ambiguous and unable to meet urgent clinical needs. Herein, this study integrates merits from previous PDT strategies and develops a cancer-targeting, activatable, biosafe photosensitizer. Owing to excellent self-assembly ability, this photosensitizer can be conveniently prepared as multifunctional nano-photosensitizers, namely MBNPs, and applied to in vivo cancer phototheranostics in "all-in-one" mode. This study successfully verifies the mechanism of MBNPs, then deploys them to cell-based and in vivo cancer PDT. Based on the unique cancer microenvironment, MBNPs achieve precise distribution, accumulation, and activation towards the tumor, releasing methylene blue as a potent photosensitizer for phototherapy. The PDT outcome demonstrates MBNPs' superior cancer specificity, remarkable PDT efficacy, and negligible toxicity. Meanwhile, in vivo NIR fluorescence and photoacoustic imaging have been utilized to guide the PDT treatment synergistically. Additionally, the biosafety of the MBNPs-based PDT treatment is ensured, thus providing potential for future clinical studies.

Titanium nanosheet as robust and biosafe drug carrier for combined photochemo cancer therapy.

Two-dimensional (2D) Titanium nanosheets (Ti NSs) have shown many excellent properties, such as nontoxicity, satisfactory photothermal conversion efficacy, etc. However, the biomedical applications of Ti NSs have not been intensively investigated. Herein, we synthesized a multifunctional Ti NS drug delivery system modified with polydopamine/polyethylene glycol (Ti@PDA-PEG) and applied simultaneously for photothermal therapy and chemotherapy. Doxorubicin (DOX) was utilized as a model drug. Ti@PDA-PEG NS shows an ultrahigh antitumor drug DOX loading (Ti@PDA-PEG-DOX). The prepared Ti@PDA-PEG-DOX NS as robust drug delivery system demonstrates great stability and excellent multi-response drug-release capabilities, including pH-responsive and near-infrared -responsive behavior and obviously high photothermal efficiency. Both in vitro and in vivo experimental results have shown high biosafety and outstanding antitumor effects. Therefore, this work exhibits the enormous potential of a multifunctional platform in the treatment of tumors and may stimulate interest in the exploration of other new 2D nanomaterials for biomedical applications.

Radiolytic synthesis and characterization of selenium nanoparticles: comparative biosafety evaluation with selenite and ionizing radiation.

The goal of this work is use a green chemistry route to synthesize selenium nanoparticles (SeNPs) that do not trigger oxidative stress, typical of metallic, oxide metallic and carbonaceous nanostructures, and supply the same beneficial effects as selenium nanostructures. SeNPs were synthesized using a radiolytic method involving irradiating a solution containing sodium selenite (Se4+) as the precursor in 1% Yeast extract, 2% Peptone, 2% Glucose (YPG) liquid medium with gamma-rays (60Cobalt). The method did not employ any hazardous reducing agents. Saccharomyces cerevisiae cells were incubated with 1 mM SeNPs for 24 h and/or then challenged with 400 Gy of ionizing radiation were assessed for viability and biomarkers of oxidative stress: lipid peroxidation, protein carbonylation, free radical generation, and total sulfhydryl content. Spherical SeNPs with variable diameters (from 100 to 200 nm) were formed after reactions of sodium selenite with hydrated electrons (eaq-) and hydrogen radicals (H·). Subsequent structural characterizations indicated an amorphous structure composed of elemental selenium (Se0). Compared to 1 mM selenite, SeNPs were considered safe and less toxic to Saccharomyces cerevisiae cells as did not elicit significant modifications in cell viability or oxidative stress parameters except for increased protein carbonylation. Furthermore, SeNPs treatment afforded some protection against ionizing radiation exposure. SeNPs produced using green chemistry attenuated the reactive oxygen species generation after in vitro ionizing radiation exposure opens up tremendous possibilities for radiosensitizer development.

Larvicidal and repellent activity of N-methyl-1-adamantylamine and oleic acid a major derivative of bael tree ethanol leaf extracts against dengue mosquito vector and their biosafety on natural predator.

Aegle marmelos (L.) Correa belongs to the family Rutaceae is generally known as "bael fruit tree" occuring across the south Asian countries. The current investigation screened the main derivatives from crude ethanolic extracts of the Bael tree leaf and evaluated activity effects on the larvae and adults of Aedes aegypti (L.) Dengue vector mosquito and a non-target aquatic predator. The GC-MS results showed that the peak area was found to be profound in N-methyl-1-adamantaneacetamide (N-M 1a) followed by oleic acid (OA) with 63.08 and 11.43% respectively. The larvicidal activity against the fourth instar larvae and the crude Ex-Am showed prominent mortality rate (93.60%) at the maximum dosage of 100 ppm. The mortality rate of N-M 1a and OA was occurred at 10 ppm (97.73%) and 12 ppm (95.4%). The repellent activity was found to be prominent at crude Ex-Am (50 ppm) as compared to the pure compounds (N-m 1a and OA) with maximum protection time up to 210 min. The non-target screening of Ex-Am, N-M 1a, and OA on mosquito predator Tx. splendens showed that they are scarcely toxic even at the maximum dosage of 1000 ppm (34.13%), 100 ppm (27.3%), and 120 ppm (31.3%) respectively. Thus, the present investigation clearly proved that the crude Ex-Am and their major derivatives Nm 1-a and OA showed their acute larval toxicity as well as potential mosquito repellent against the dengue mosquito and eco-safety against the mosquito predator.

National Biosafety Management System: A Combined Framework Approach Based on 15 Key Elements.

The pervasive nature of infections causing major outbreaks have elevated biosafety and biosecurity as a fundamental component for resilient national laboratory systems. In response to international health security demands, the Global Health Security Agenda emphasizes biosafety as one of the prerequisites to respond effectively to infectious disease threats. However, biosafety management systems (BMS) in low-medium income countries (LMIC) remain weak due to fragmented implementation strategies. In addition, inefficiencies in implementation have been due to limited resources, inadequate technical expertise, high equipment costs, and insufficient political will. Here we propose an approach to developing a strong, self-sustaining BMS based on extensive experience in LMICs. A conceptual framework incorporating 15 key components to guide implementers, national laboratory leaders, global health security experts in building a BMS is presented. This conceptual framework provides a holistic and logical approach to the development of a BMS with all critical elements. It includes a flexible planning matrix with timelines easily adaptable to different country contexts as examples, as well as resources that are critical for developing sustainable technical expertise.

Scientific validation of the antimicrobial and antiproliferative potential of Clerodendrum serratum (L.) Moon, its phytoconstituents and their biosafety by acute oral toxicity study.

The screening of aqueous extract of Clerodendrum serratum revealed its broad-spectrum antimicrobial potential against Gram positive, Gram negative bacteria, and yeast. Optimizing the extraction strategies, revealed 15% concentration of aqueous extract prepared at 40 °C by extracting for 40 min, as optimum parameters and its statistical optimization by Box-Behnken design led to 1.16-1.35 folds enhancement in activity. Organic solvent extraction further improved the activity where methanol proved to be the best organic extractant which was effective against all the 13 pathogens tested with inhibition zone ranging from 14 to 32 mm. Minimum Inhibitory Concentration (MIC) study endorsed the methanolic extract to be the best organic extractant, as it showed the lowest MIC (0.5-10 mg/ml) in comparison to aqueous extract (1-10 mg/ml) as well as Partially Purified Phytoconstituents i.e., flavonoids (1-5 mg/ml), diterpenes (5-10 mg/ml) and cardiac glycosides (5-10 mg/ml). All these were found to be biosafe in both In-vitro (Ames and MTT assay) and In-vivo toxicity studies. Acute oral toxicity testing of flavonoids (2000 mg/ml) on Wistar rats did not reveal any significant change in relative organ weight, biochemical, hematological parameters and organs' architecture in comparison to control. Antiproliferative potential of flavonoids against human cancerous cell lines i.e., HeLa, HCT-15, and U87-MG, further increase the importance of this plant as a promising candidate for drug development. The overall study justified the medicinal importance of this plant.

Energy-converting biomaterials for cancer therapy: Category, efficiency, and biosafety.

Energy-converting biomaterials (ECBs)-mediated cancer-therapeutic modalities have been extensively explored, which have achieved remarkable benefits to overwhelm the obstacles of traditional cancer-treatment modalities. Energy-driven cancer-therapeutic modalities feature their distinctive merits, including noninvasiveness, low mammalian toxicity, adequate therapeutic outcome, and optimistical synergistic therapeutics. In this advanced review, the prevailing mainstream ECBs can be divided into two sections: Reactive oxygen species (ROS)-associated energy-converting biomaterials (ROS-ECBs) and hyperthermia-related energy-converting biomaterials (H-ECBs). On the one hand, ROS-ECBs can transfer exogenous or endogenous energy (such as light, radiation, ultrasound, or chemical) to generate and release highly toxic ROS for inducing tumor cell apoptosis/necrosis, including photo-driven ROS-ECBs for photodynamic therapy, radiation-driven ROS-ECBs for radiotherapy, ultrasound-driven ROS-ECBs for sonodynamic therapy, and chemical-driven ROS-ECBs for chemodynamic therapy. On the other hand, H-ECBs could translate the external energy (such as light and magnetic) into heat for killing tumor cells, including photo-converted H-ECBs for photothermal therapy and magnetic-converted H-ECBs for magnetic hyperthermia therapy. Additionally, the biosafety issues of ECBs are expounded preliminarily, guaranteeing the ever-stringent requirements of clinical translation. Finally, we discussed the prospects and facing challenges for constructing the new-generation ECBs for establishing intriguing energy-driven cancer-therapeutic modalities. This article is categorized under: Nanotechnology Approaches to Biology >Nanoscale Systems in Biology.

Effet du confinement de la pandémie à COVID-19 sur les besoins nutritionnels dans une population adulte active et chez des personnes en âge de retraite à Brazzaville, République du Congo / Impact of COVID-19 lockdown on nutritional status of active adults and retirement-age population in Brazzaville, Republic of Congo

Contexte & objectif. La dimension nutritionnelle du confinement instauré à l'occasion de la pandémie COVID-19 n'a pas encore était étudiée en milieu africain. La présente étude a pour objectifs d'identifier et analyser les caractéristiques nutritionnelles chez l'adulte actif et la personne âgée congolais pour dépister d'éventuelles carences. Méthodes. Dans une enquête transversale menée lors du second confinement entre avril et mai 2020, quelques ménages de Bacongo (Brazzaville, Congo) recrutés aléatoirement, ont été interviewés sur base d'un questionnaire de type alimentaire quantitatif. Elle portait sur la nature et la quantité des aliments consommés durant toute la journée, du lever au coucher. Les apports quotidiens ont été calculés, et rendus en termes de % d'énergie fournie respectivement par les glucides, les lipides et les protides ; ainsi que les oligo-éléments, et les vitamines (A, B et C). Résultats. La valeur nutritionnelle moyenne globale était de 2123,5 ± 494,5 Kcal, chez les 183 sujets inclus (107 adultes en activité professionnelle âgés entre 31 et 59 and et 76 personnes âgées de 66 à 80 ans). Spécifiquement, les besoins en glucides étaient couverts à hauteur de 81,5 %, tandis que ceux en protéines et en lipides étaient insuffisants, respectivement de l'ordre 33,5 g/j et 59,5 g/j en moyenne. Les apports en calcium, phosphore, et magnésium, étaient conformes aux normes recommandées, étant respectivement : de 613,9 mg, 709,8 mg et 267,5 mg. Les apports en fer se situaient à la limite inférieure de la normale (7,7 mg) chez les sujets âgés de plus de 66 ans. Les apports en vitamines A et C étaient satisfaisants, tandis qu'un risque de carence était observé pour les vitamines B1 et B2, dans le groupe des sujets âgés de 31 à 59 ans (0,17 mg et 0,58 mg). Conclusion. Ces observations suggèrent un effet négatif du confinement dans le domaine nutritionnel, justifiant des stratégies adaptées de supplémentation alimentaire, en vue de renforcer les capacités immunitaires dans la population exposée.

Context & objective. Nutritional impact of lockdown due to the COVID-19 pandemic has not yet been studied in African environment. This study aimed to analyze the nutritional characteristics of active adults and the elderly Congolese to screen for possible deficiencies. Methods. The cross-sectional survey was carried out between April and May 2020, during the 2nd Covid-19 lockdown. Few households in Bacongo (Brazzaville) were randomly recruited and interviewed, using a quantitative food-type questionnaire, adressing the nature and quantity of food consumed throughout the day. Daily intakes were measured and reported as percentage of energy supplied respectively by carbohydrates, lipids and proteins; as well as trace elements, and few vitamins. Results. The overall average nutritional value around 2123.5 ± 494.5 kcal reflects an insufficient intake; specifically for proteins (33,5g/d) and fat (59,5g/d) requirements, except for carbohydrates (81,5%). The intakes of calcium (613.9 mg), phosphorus (709,8 mg), and magnesium (267,5 mg) met the recommended standards. Iron intakes were at the lower limit of normal (7.7 mg) in subjects aged more than 66 yrs to. Vitamin intakes were relevant for vitamins A and C, while slightly deficient in subjects aged 31- 59 yrs for vitamins B1 and B2. Conclusion. The present observations suggest a negative nutritional impact of lockdown, highlighting the need for targeted nutritional strategies of food supplementation.

Bioprospecting the antimicrobial, antibiofilm and antiproliferative activity of Symplocos racemosa Roxb. Bark phytoconstituents along with their biosafety evaluation and detection of antimicrobial components by GC-MS.

BACKGROUND: Plants provide a ray of hope to combat the ever increasing antibiotic resistance and Symplocos racemosa is a valuable medicinal plant. The study focused on highlighting the importance of this plant's phytoconstituents as potential source of novel antimicrobials against planktonic as well as biofilm forming microorganisms, along with their antiproliferative activity. The biosafety of the phytoconstituents was also established, followed by detection of probable antimicrobial components. METHODS: The best organic extractant and major groups of phytoconstituents were tested for their antimicrobial activity against reference microbial strains and drug-resistant clinical isolates. The anti-proliferative potential of the most active group of phytoconstituents was evaluated against cancerous cell lines. The in vitro biosafety of phytoconstituents was evaluated by Ames and MTT assay, while in vivo biosafety of the most active phytoconstituents, i.e., flavonoids was determined by acute oral toxicity. Further, the probable antimicrobial components in the flavonoids were detected by TLC and GC-MS. RESULTS: Ethyl acetate extract was the most effective among various organic extracts, whereas phytoconstituents such as flavonoids, cardiac glycosides, saponins, tannins, triterpenes and phytosterols were the major groups present, with flavonoids being the most potent antimicrobials. The phytoconstituents displayed a significant antibiofilm potential, as exhibited by inhibition of initial cell attachment, disruption of the pre-formed biofilms and reduced metabolic activity of biofilms. The phytoconstituents were significantly active against the drug-resistant strains of E.coli, MRSA and Salmonella spp. Further, flavonoids showed significant cytotoxic effect against the cancerous cell lines but were non-cytotoxic against Vero (normal) cell line. All the test preparations were biosafe, as depicted by the Ames test and MTT assay. Also, flavonoids did not induce any abnormality in body weight, clinical signs, biochemical parameters and organs' histopathology of the Swiss albino mice during in vivo acute oral toxicity studies. The flavonoids were resolved into 4 bands (S1-S4), where S3 was the most active and its GC-MS analysis revealed the presence of a number of compounds, where Bicyclo [2.2.1]heptan-2-one,1,7,7-trimethyl-, (1S)- was the most abundant. CONCLUSIONS: These findings suggest that the phytoconstituents from Symplocos racemosa bark could act as potential source of antimicrobial as well as antiproliferative metabolites.

Biosafety and biocompatibility assessment of Prussian blue nanoparticles in vitro and in vivo.

Aim: To investigate the effects of the different morphological characteristics of Prussian blue nanoparticles (PB NPs) on their biocompatibility and biosafety. Materials & methods: PB NPs with different sizes, shapes and charges were synthesized and their biosafety and biocompatibility performance were systematically compared in vitro and in vivo. Results: Increased size and positive charge of PB NPs adversely affected cell viability, while improving their peroxidase activity and photothermal conversion efficiency. In vivo analysis demonstrated good biocompatibility of PB NPs, without retention in the organs, but increased size retarded their metabolism. Meanwhile, increased size and positive charge adversely affected hepatic and renal function. Conclusion: This comprehensive exploration of biosafety and biocompatibility provides strong evidences for the use of PB NPs as nanodrug carrier and/or imaging agent.

Seed biopriming with P- and K-solubilizing Enterobacter hormaechei sp. improves the early vegetative growth and the P and K uptake of okra (Abelmoschus esculentus) seedling.

Limited information is available that seed biopriming with plant growth-promoting Enterobacter spp. play a prominent role to enhance vegetative growth of plants. Contrary to Enterobacter cloacae, Enterobacter hormaechei is a less-studied counterpart despite its vast potential in plant growth-promotion mainly through the inorganic phosphorus (P) and potassium (K) solubilization abilities. To this end, 18 locally isolated bacterial pure cultures were screened and three strains showed high P- and K-solubilizing capabilities. Light microscopy, biochemical tests and 16S rRNA gene sequencing revealed that strains 15a1 and 40a were closely related to Enterobacter hormaechei while strain 38 was closely related to Enterobacter cloacae (Accession number: MN294583; MN294585; MN294584). All Enterobacter spp. shared common plant growth-promoting traits, namely nitrogen (N2) fixation, indole-3-acetic acid production and siderophore production. The strains 38 and 40a were able to produce gibberellic acid, while only strain 38 was able to secrete exopolysaccharide on agar. Under in vitro germination assay of okra (Abelmoschus esculentus) seeds, Enterobacter spp. significantly improved overall germination parameters and vigor index (19.6%) of seedlings. The efficacy of root colonization of Enterobacter spp. on the pre-treated seedling root tips was confirmed using Scanning Electron Microscopy (SEM). The pot experiment of bioprimed seeds of okra seedling showed significant improvement of the plant growth (> 28%) which corresponded to the increase of P and K uptakes (> 89%) as compared to the uninoculated control plants. The leaf surface area and the SPAD chlorophyll index of bioprimed plants were increased by up to 29% and 9% respectively. This report revealed that the under-explored species of P- and K-solubilizing Enterobacter hormaechei sp. with multiple plant beneficial traits presents a great potential sustainable approach for enhancement of soil fertility and P and K uptakes of plants.

A novel biosafety level 2 compliant tuberculosis infection model using a ΔleuDΔpanCD double auxotroph of Mycobacterium tuberculosis H37Rv and Galleria mellonella.

Mammalian infection models have contributed significantly to our understanding of the host-mycobacterial interaction, revealing potential mechanisms and targets for novel antimycobacterial therapeutics. However, the use of conventional mammalian models such as mice, are typically expensive, high maintenance, require specialized animal housing, and are ethically regulated. Furthermore, research using Mycobacterium tuberculosis (MTB), is inherently difficult as work needs to be carried out at biosafety level 3 (BSL3). The insect larvae of Galleria mellonella (greater wax moth), have become increasingly popular as an infection model, and we previously demonstrated its potential as a mycobacterial infection model using Mycobacterium bovis BCG. Here we present a novel BSL2 complaint MTB infection model using G. mellonella in combination with a bioluminescent ΔleuDΔpanCD double auxotrophic mutant of MTB H37Rv (SAMTB lux) which offers safety and practical advantages over working with wild type MTB. Our results show a SAMTB lux dose dependent survival of G. mellonella larvae and demonstrate proliferation and persistence of SAMTB lux bioluminescence over a 1 week infection time course. Histopathological analysis of G. mellonella, highlight the formation of early granuloma-like structures which matured over time. We additionally demonstrate the drug efficacy of first (isoniazid, rifampicin, and ethambutol) and second line (moxifloxacin) antimycobacterial drugs. Our findings demonstrate the broad potential of this insect model to study MTB infection under BSL2 conditions. We anticipate that the successful adaptation and implementation of this model will remove the inherent limitations of MTB research at BSL3 and increase tuberculosis research output.

A High-Throughput HIV-1 Drug Screening Platform, Based on Lentiviral Vectors and Compatible with Biosafety Level-1.

HIV-1 infection is a complex, multi-step process involving not only viral, but also multiple cellular factors. To date, drug discovery methods have primarily focused on the inhibition of single viral proteins. We present an efficient and unbiased approach, compatible with biosafety level 1 (BSL-1) conditions, to identify inhibitors of HIV-1 reverse transcription, intracellular trafficking, nuclear entry and genome integration. Starting with a fluorescent assay setup, we systematically improved the screening methodology in terms of stability, efficiency and pharmacological relevance. Stability and throughput were optimized by switching to a luciferase-based readout. BSL-1 compliance was achieved without sacrificing pharmacological relevance by using lentiviral particles pseudo-typed with the mouse ecotropic envelope protein to transduce human PM1 T cells gene-modified to express the corresponding murine receptor. The cellular assay was used to screen 26,048 compounds selected for maximum diversity from a 200,640-compound in-house library. This yielded z' values greater than 0.8 with a hit rate of 3.3% and a confirmation rate of 50%. We selected 93 hits and enriched the collection with 279 similar compounds from the in-house library to identify promising structural features. The most active compounds were validated using orthogonal assay formats. The similarity of the compound profiles across the different platforms demonstrated that the reported lentiviral assay system is a robust and versatile tool for the identification of novel HIV-1 inhibitors.

ICG-Conjugated and 125 I-Labeled Polymeric Micelles with High Biosafety for Multimodality Imaging-Guided Photothermal Therapy of Tumors.

Noninvasive multimodality imaging-guided precision photothermal therapy (PTT) is proven to be an effective strategy for tumor theranostics by integrating diagnostics and therapeutics in one nanoplatform. In this study, indocyanine green (ICG)-conjugated and radionuclide iodine-125 (125 I)-labeled polymeric micelles (PEG-PTyr(125 I)-ICG PMs) are strategically prepared by the self-assembly of the ICG-decorated amphiphilic diblock polymer poly(ethylene glycol)-poly(l-tyrosine-125 I)-(indocyanine green) (PEG-PTyr(125 I)-ICG). The as-prepared polymeric micelles exhibit favorable biocompatibility, excellent size/photo/radiolabel stability, a high-photothermal conversion efficiency, a passive tumor-targeting ability, and a fluorescence (FL)/photoacoustic (PA)/single photon emission computed tomography (SPECT) imaging property. After tail intravenous injection, the polymeric micelles can efficiently accumulate at the tumor site and present comprehensive FL/PA/SPECT images with a high sensitivity, excellent spatial resolution, and unlimited tissue penetration under near-infrared (NIR) irradiation. Upon 808 nm laser irradiation, the subsequent precision PTT of tumors can be achieved with minimal cumulative side effects. Thus, this capable multifunctional nanoplatform with simple components and preparation procedures for FL/PA/SPECT multimodality imaging-guided PTT can be a potential candidate for clinical tumor theranostics.

Odontologia em Tempos de COVID-19: Revisão Integrativa e Proposta de Protocolo para Atendimento nas Unidades de Saúde Bucal da Polícia Militar do Estado do Rio de Janeiro - PMERJ / Dentistry During the COVID-19 Pandemic: Integrative Review and Proposed Protocol for the Rio de Janeiro State Military Police Dental Care Units

Objetivo: sistematizar a produção bibliográfica sobre as recomendações, práticas e cuidados adotados no atendimento odontológico em tempos de COVID-19, assim como, propor um protocolo de atendimento odontológico nas unidades de saúde bucal da Polícia Militar do Estado do Rio de Janeiro a partir das evidências encontradas na literatura. Material e Métodos: foi realizada uma busca bibliográfica no dia 11 de abril de 2020 em bases bibliográficas eletrônicas brasileiras e internacionais (Portal Regional da Biblioteca Virtual em Saúde, Web of Science e Pubmed), a partir da estratégia de busca ("COVID-19" AND "dentistry"), entre estudos publicadas nos anos de 2019 e 2020. Após aplicados os critérios de inclusão e exclusão dos documentos, 18 estudos foram considerados elegíveis para a realização da revisão. Resultados: a partir das evidências científicas encontradas nos estudos, foi construída uma proposta de protocolo para o atendimento odontológico nas unidades de saúde da Polícia Militar do Estado do Rio de Janeiro, assim como em qualquer outra unidade de saúde bucal. Conclusão: durante o período de surto epidêmico os atendimentos devem restringir-se às urgências e emergências odontológicas. O Cirurgião-Dentista deve redobrar a atenção à rotina de biossegurança como: lavagem rigorosa das mãos com água e sabão e/ou 'álcool gel a 70%', uso correto de todo equipamento de proteção individual e sua troca a cada paciente. Recomenda-se o tempo de 3 horas entre os atendimentos quando houver produção de aerossol, a higienização de todas as superfícies do consultório com hipoclorito de sódio a 0,1% ou 'álcool 70%', esterilização de todo instrumental e o descarte adequado dos resíduos.

Objective: to collate the literature that contains recommendations, best practices, and infection control measures for dental health care during the COVID-19 pandemic and, based on this evidence, to propose a protocol for use at the Rio de Janeiro State Military Police dental health care units. Materials and Methods: search of the regional VHL Network Portal, Web of Science, and Pubmed databases using the search query ("covid19" AND "dentistry") to retrieve studies published in 2019 and 2020. After applying the inclusion and exclusion criteria, 18 were found to be eligible for the review. Results: from the scientific evidence reported in the retrieved documents, an infection control protocol was proposed for use at the Rio de Janeiro State Military Police dental care units, which could be applied to any dental health setting. Conclusion: while the epidemic continues, only urgent and emergency dental care should be provided. The dental surgeon should adopt enhanced biosecurity measures, namely: rigorous hand sanitizing with soap and water and/or 70% alcohol hand sanitizer; correct use of complete personal protective equipment (PPE), and discarding of PPE after each patient; allowing three hours to elapse between patients after aerosol-generating procedures; cleaning of all surfaces with 0.1% sodium hypochlorite or 70% ethanol; sterilization of all instruments; and adequate disposal of all waste.

Uso dos Equipamentos de Proteção Individual no Atendimento Odontológico Durante Surto da COVID-19 e Alternativas em Períodos de Desabastecimento: Revisão Integrativa / Use of Personal Protective Equipment in Dental Care During COVID-19 Outbreaks and Options During Supply Shortages: An Integrative Review

Objetivo: sistematizar a produção bibliográfica sobre as recomendações para uso, uso prolongado, reuso e descontaminação de equipamentos de proteção individual (EPI) no atendimento odontológico em período de surto epidêmico da COVID-19 a partir das evidências encontradas na literatura. Material e Métodos: foi realizada uma busca bibliográfica no dia 1 de maio de 2020 em bases bibliográficas eletrônicas brasileiras e internacionais (Portal Regional da Biblioteca Virtual em Saúde, Web of Science e Pubmed), a partir da estratégia de busca ("individual protective equipment" AND "covid-19"), entre estudos publicados nos anos de 2015 a 2020. Foram também analisados documentos de órgãos de vigilância sanitária de diferentes países e recomendações da Associação Americana de Odontologia. Após aplicados os critérios de inclusão e exclusão dos documentos, 20 estudos foram considerados elegíveis para a realização da revisão. Resultados: Há uma escassez de publicações que relacionem a odontologia e o uso de EPI durante a pandemia. O uso prolongado/reuso limitado de respiradores (N95, PFF2, PFF3) pode ser recomendado em períodos de grave desabastecimento de EPIs desde que a sua integridade e capacidade de vedação estejam mantidas. Os aventais de tecido não tecido, máscaras cirúrgicas, luvas e gorros são considerados equipamentos de uso único. Os protetores oculares podem ser reusados após limpeza e desinfecção. Conclusão: Em períodos de surtos epidêmicos da SARS-CoV-2 recomendamos para atendimento odontológico com geração de aerossol o uso de respiradores do tipo N95, PFF2, PFF3 ou equivalente, protetor facial que pode ser reusado após limpeza e desinfecção e o uso de avental impermeável, luvas e gorro que devem ser descartados a cada paciente

Objective: to collate the recommendations on the use, extended use, reuse, and decontamination of personal protective equipment (PPE) in dental care during the COVID-19 outbreak, based on evidence found in the literature. Materials and Methods: searches were made of the following Brazilian and international databases on May 1, 2020: the Virtual Health Library Regional Portal, the Web of Science, and PubMed. The search strategy was based on the query ("individual protective equipment" AND "COVID-19") and retrieved publications from 2015 to 2020. Oficial infection prevention and control documents from different countries were also analyzed, as well as the recommendations of the American Dental Association. After applying the inclusion and exclusion criteria, a total of 20 studies were found to be eligible for the review. Results: there is a dearth of publications relating dentistry and PPE use during the pandemic. The extended use and reuse of respirators (N95, FFP2, FFP3) may be recommended during severe shortages, provided they are not damaged and they seal adequately. Nonwoven fabric gowns, surgical masks, gloves, and caps are singleuse PPE. Eye protection may be reused after cleaning and disinfection. Conclusion: during the epidemic of SARS-CoV-2 we recommend wearing a N95, FFP2, FFP3 or equivalent respirator during aerosol-generating procedures, a face shield, which may be reused after cleaning and disinfection, and an impermeable gown, gloves, and cap, which should be discarded between patients