Recent advances in engineered polymeric materials for efficient photodynamic inactivation of bacterial pathogens.

Nowadays, infectious diseases persist as a global crisis by causing significant destruction to public health and the economic stability of countries worldwide. Especially bacterial infections remain a most severe concern due to the prevalence and emergence of multi-drug resistance (MDR) and limitations with existing therapeutic options. Antibacterial photodynamic therapy (APDT) is a potential therapeutic modality that involves the systematic administration of photosensitizers (PSs), light, and molecular oxygen (O2) for coping with bacterial infections. Although the existing porphyrin and non-porphyrin PSs were effective in APDT, the poor solubility, limited efficacy against Gram-negative bacteria, and non-specific distribution hinder their clinical applications. Accordingly, to promote the efficiency of conventional PSs, various polymer-driven modification and functionalization strategies have been adopted to engineer multifunctional hybrid phototherapeutics. This review assesses recent advancements and state-of-the-art research in polymer-PSs hybrid materials developed for APDT applications. Further, the key research findings of the following aspects are considered in-depth with constructive discussions: i) PSs-integrated/functionalized polymeric composites through various molecular interactions; ii) PSs-deposited coatings on different substrates and devices to eliminate healthcare-associated infections; and iii) PSs-embedded films, scaffolds, and hydrogels for regenerative medicine applications.

Photoacoustic nanodroplets for oxygen enhanced photodynamic therapy of cancer.

Photodynamic therapy (PDT) is a well-known cancer therapy that utilizes light to excite a photosensitizer and generate cytotoxic reactive oxygen species (ROS). The efficacy of PDT primarily depends on the photosensitizer and oxygen concentration in the tumor. Hypoxia in solid tumors promotes treatment resistance, resulting in poor PDT outcomes. Hence, there is a need to combat hypoxia while delivering sufficient photosensitizer to the tumor for ROS generation. Here we showcase our unique theranostic perfluorocarbon nanodroplets as a triple agent carrier for oxygen, photosensitizer, and indocyanine green that enables light triggered spatiotemporal delivery of oxygen to the tumors. We evaluated the characteristics of the nanodroplets and validated their ability to deliver oxygen via photoacoustic monitoring of blood oxygen saturation and subsequent PDT efficacy in a murine subcutaneous tumor model. The imaging results were validated with an oxygen sensing probe, which showed a 9.1 fold increase in oxygen content inside the tumor, following systemic administration of the nanodroplets. These results were also confirmed with immunofluorescence. In vivo studies showed that nanodroplets held higher rates of treatment efficacy than a clinically available benzoporphyrin derivative formulation. Histological analysis showed higher necrotic area within the tumor with perfluoropentane nanodroplets. Overall, the photoacoustic nanodroplets can significantly enhance image-guided PDT and has demonstrated substantial potential as a valid theranostic option for patient-specific photodynamic therapy-based treatments.

SARS-CoV-2 in environmental perspective: Occurrence, persistence, surveillance, inactivation and challenges.

The unprecedented global spread of the severe acute respiratory syndrome (SARS) caused by SARS-CoV-2 is depicting the distressing pandemic consequence on human health, economy as well as ecosystem services. So far novel coronavirus (CoV) outbreaks were associated with SARS-CoV-2 (2019), middle east respiratory syndrome coronavirus (MERS-CoV, 2012), and SARS-CoV-1 (2003) events. CoV relates to the enveloped family of Betacoronavirus (ßCoV) with positive-sense single-stranded RNA (+ssRNA). Knowing well the persistence, transmission, and spread of SARS-CoV-2 through proximity, the faecal-oral route is now emerging as a major environmental concern to community transmission. The replication and persistence of CoV in the gastrointestinal (GI) tract and shedding through stools is indicating a potential transmission route to the environment settings. Despite of the evidence, based on fewer reports on SARS-CoV-2 occurrence and persistence in wastewater/sewage/water, the transmission of the infective virus to the community is yet to be established. In this realm, this communication attempted to review the possible influx route of the enteric enveloped viral transmission in the environmental settings with reference to its occurrence, persistence, detection, and inactivation based on the published literature so far. The possibilities of airborne transmission through enteric virus-laden aerosols, environmental factors that may influence the viral transmission, and disinfection methods (conventional and emerging) as well as the inactivation mechanism with reference to the enveloped virus were reviewed. The need for wastewater epidemiology (WBE) studies for surveillance as well as for early warning signal was elaborated. This communication will provide a basis to understand the SARS-CoV-2 as well as other viruses in the context of the environmental engineering perspective to design effective strategies to counter the enteric virus transmission and also serves as a working paper for researchers, policy makers and regulators.

Alternaria host-specific (HSTs) toxins: An overview of chemical characterization, target sites, regulation and their toxic effects.

Alternaria causes pathogenic disease on various economically important crops having saprophytic to endophytic lifecycle. Pathogenic fungi of Alternaria species produce many primary and secondary metabolites (SMs). Alternaria species produce more than 70 mycotoxins. Several species of Alternaria produce various phytotoxins that are host-specific (HSTs) and non-host-specific (nHSTs). These toxins have various negative impacts on cell organelles including chloroplast, mitochondria, plasma membrane, nucleus, Golgi bodies, etc. Non-host-specific toxins such as tentoxin (TEN), Alternaric acid, alternariol (AOH), alternariol 9-monomethyl ether (AME), brefeldin A (dehydro-), Alternuene (ALT), Altertoxin-I, Altertoxin-II, Altertoxin-III, zinniol, tenuazonic acid (TeA), curvularin and alterotoxin (ATX) I, II, III are known toxins produced by Alternaria species. In other hand, Alternaria species produce numerous HSTs such as AK-, AF-, ACT-, AM-, AAL- and ACR-toxin, maculosin, destruxin A, B, etc. are host-specific and classified into different family groups. These mycotoxins are low molecular weight secondary metabolites with various chemical structures. All the HSTs have different mode of actions, biochemical reactions, and signaling mechanisms to causes diseases in the host plants. These HSTs have devastating effects on host plant tissues by affecting biochemical and genetic modifications. Host-specific mycotoxins such as AK-toxin, AF-toxin, and AC-toxin have the devastating effect on plants which causes DNA breakage, cytotoxic, apoptotic cell death, interrupting plant physiology by mitochondrial oxidative phosphorylation and affect membrane permeability. This article will elucidate an understanding of the disease mechanism caused by several Alternaria HSTs on host plants and also the pathways of the toxins and how they caused disease in plants.

Differential ROS Generation in Response to Stress in Symbiodinium spp.

Oxidative stress inside cells occurs when the production of reactive oxygen species (ROS) is no longer efficiently counterbalanced by the generation of antioxidants. In this study, we measured the intracellular production of ROS, including hydrogen peroxide (H2O2), superoxide (O2-), and singlet oxygen (1O2), in cultured dinoflagellates of the genus Symbiodinium under thermal and oxidative stress. ROS tagged with fluorescent probes were measured by flow cytometry. Dissimilar Symbiodinium internal transcribed spacer 2 (ITS2) clades or phylotypes (A1, B2, E, F1) produced ROS in different quantities in response to stress. For example, when comparing the control (26 °C) to the high-temperature treatment (35 °C), Symbiodinium E showed no change in the intracellular concentrations of any of the ROS; but phylotype A1 displayed a 10-fold increase in the overall ROS concentration and a 4-fold increase in O2-. Under oxidative stress, when 8 mmol l-1 H2O2 was added to the cells, these same two Symbiodinium phylotypes increased their overall concentrations of ROS, but only Symbiodinium E showed an increase in the concentrations of O2- (2×) and 1O2 (3×). Therefore, not only were the stress responses of the various Symbiodinium phylotypes different but also the responses of individual phylotypes to thermal and oxidative stress were different in terms of ROS production. Variation in the quality and quantity of ROS generation and its implications for subsequent antioxidant production suggest that different stress mechanisms are at play. While our experiments were done under laboratory conditions that did not necessarily mirror ecological ones, these results provide new insight into processes inside Symbiodinium cells during stress events and add new explanations for a phylotype's susceptibility to stress.

Discovery of direct inhibitors of Keap1-Nrf2 protein-protein interaction as potential therapeutic and preventive agents.

The Keap1-Nrf2-ARE pathway is an important antioxidant defense mechanism that protects cells from oxidative stress and the Keap1-Nrf2 protein-protein interaction (PPI) has become an important drug target to upregulate the expression of ARE-controlled cytoprotective oxidative stress response enzymes in the development of therapeutic and preventive agents for a number of diseases and conditions. However, most known Nrf2 activators/ARE inducers are indirect inhibitors of Keap1-Nrf2 PPI and they are electrophilic species that act by modifying the sulfhydryl groups of Keap1׳s cysteine residues. The electrophilicity of these indirect inhibitors may cause "off-target" side effects by reacting with cysteine residues of other important cellular proteins. Efforts have recently been focused on the development of direct inhibitors of Keap1-Nrf2 PPI. This article reviews these recent research efforts including the development of high throughput screening assays, the discovery of peptide and small molecule direct inhibitors, and the biophysical characterization of the binding of these inhibitors to the target Keap1 Kelch domain protein. These non-covalent direct inhibitors of Keap1-Nrf2 PPI could potentially be developed into effective therapeutic or preventive agents for a variety of diseases and conditions.