Two-dimensional molybdenum disulfide (MoS2) based nanosheets functionalized or loaded with an antimicrobial agent have recently attracted attention as highly efficient antibacterial agent. MoS2 sheets act as the photothermal transducers in inducing bacterial cell death on impingement of NIR radiation or enabled cell inactivation by wrapping around the cells. However, the intrinsic ability of MoS2 to act as an effective antibacterial agent without the use of any external stimuli or antimicrobial agent is still not well explored. This study provides a detailed mechanism of antibacterial action of chitosan exfoliated MoS2 nanosheets (CS-MoS2) by deciphering the key events happening both at the membrane surface and inside the bacteria as a result of interaction of bacterial cells with the nanosheets. A simple, green, one-step process was employed for synthesizing stable and positively charged MoS2 nanosheets. The prepared nanosheets showed excellent bactericidal activity against both Gram-positive (MIC = 90 μg/mL, MBC = 120 μg/mL) and Gram-negative bacteria (MIC = 30 μg/mL, MBC = 60 μg/mL). Investigations into deciphering the mechanism of action revealed that the CS-MoS2 nanosheets interacted strongly with the bacterial cells through electrostatic interactions and caused rapid depolarization of the membranes through dent formations. On account of strong van der Waals and electrostatic forces occurring between the CS-MoS2 nanosheets and membrane phospholipid molecules, deepening of dents occurred, which resulted in complete membrane disruption and leakage of cytoplasmic contents. This led to inactivation of the bacterial respiratory pathway through inhibition of dehydrogenase enzymes and induced metabolic arrest in the cells. Simultaneously, disruption of the antioxidant defense system of the cells by increased levels of intracellular ROS subjected the cells to oxidative damage and added to the overall bactericidal action. The nanosheets also displayed antibiofilm properties and were found to be compatible with mammalian cells even at high concentrations.

The current pandemic caused by SARS-CoV-2 has seen a widespread use of personal protective equipment, especially face masks. This has created the need to develop better and reusable protective masks with built-in antimicrobial, self-cleaning, and aerosol filtration properties to prevent the transmission of air-borne pathogens such as the coronaviruses. Herein, molybdenum disulfide (MoS 2 ) nanosheets are used to prepare modified polycotton fabrics having excellent antibacterial activity and photothermal properties. Upon sunlight irradiation, the nanosheet-modified fabrics rapidly increased the surface temperature to ∼77 °C, making them ideal for sunlight-mediated self-disinfection. Complete self-disinfection of the nanosheet-modified fabric was achieved within 3 min of irradiation, making the fabrics favorably reusable upon self-disinfection. The nanosheetmodified fabrics maintained the antibacterial efficiency even after 60 washing cycles. Furthermore, the particle filtration efficiency of three-layered surgical masks was found to be significantly improved through incorporation of the MoS 2 -modified fabric as an additional layer of protective clothing, without compromising the breathability of the masks. The repurposed surgical masks could filter out around 97% of 200 nm particles and 96% of 100 nm particles, thus making them potentially useful for preventing the spread of coronaviruses (120 nm) by trapping them along with antibacterial protection against other airborne pathogens.

After injury, severed dendrites and axons expose the “eat-me” signal phosphatidylserine (PS) on their surface while they break down. The degeneration of injured axons is controlled by a conserved Wallerian degeneration (WD) pathway, which is thought to activate neurite self-destruction through Sarm-mediated nicotinamide adenine dinucleotide (NAD+) depletion. While neurite PS exposure is known to be affected by genetic manipulations of NAD+, how the WD pathway coordinates both neurite PS exposure and self-destruction and whether PS-induced phagocytosis contributes to neurite breakdown in vivo remain unknown. Here, we show that in Drosophila sensory dendrites, PS exposure and self-destruction are two sequential steps of WD resulting from Sarm activation. Surprisingly, phagocytosis is the main driver of dendrite degeneration induced by both genetic NAD+ disruptions and injury. However, unlike neuronal Nmnat loss, which triggers PS exposure only and results in phagocytosis-dependent dendrite degeneration, injury activates both PS exposure and self-destruction as two redundant means of dendrite degeneration. Furthermore, the axon-death factor Axed is only partially required for self-destruction of injured dendrites, acting in parallel with PS-induced phagocytosis. Lastly, injured dendrites exhibit a unique rhythmic calcium-flashing that correlates with WD. Therefore, both NAD+-related general mechanisms and dendrite-specific programs govern PS exposure and self-destruction in injury-induced dendrite degeneration in vivo.

BackgroundThe progressive neurodegenerative disorder Alzheimer’s disease (AD) manifests as loss of cognitive functions, and finally leads to death of the affected individual. AD may result from accumulation of amyloid plaques. These amyloid plaques comprising of amyloid-beta 42 (Aβ42) polypeptides results from the improper cleavage of amyloid precursor protein (APP) in the brain. The Aβ42 plaques have been shown to disrupt the normal cellular processes and thereby trigger abnormal signaling which results in the death of neurons. However, the molecular-genetic mechanism(s) responsible for Aβ42 mediated neurodegeneration is yet to be fully understood.Methodology/Principal FindingsWe have utilized Gal4/UAS system to develop a transgenic fruit fly model for Aβ42 mediated neurodegeneration. Targeted misexpression of human Aβ42 in the differentiating photoreceptor neurons of the developing eye of transgenic fly triggers neurodegeneration. This progressive neurodegenerative phenotype resembles Alzheimer’s like neuropathology. We identified a histone acetylase, CREB Binding Protein (CBP), as a genetic modifier of Aβ42 mediated neurodegeneration. Targeted misexpression of CBP along with Aβ42 in the differentiating retina can significantly rescue neurodegeneration. We found that gain-of-function of CBP rescues Aβ42 mediated neurodegeneration by blocking cell death. Misexpression of Aβ42 affects the targeting of axons from retina to the brain but misexpression of full length CBP along with Aβ42 can restore this defect. The CBP protein has multiple domains and is known to interact with many different proteins. Our structure function analysis using truncated constructs lacking one or more domains of CBP protein, in transgenic flies revealed that Bromo, HAT and polyglutamine (BHQ) domains together are required for the neuroprotective function of CBP. This BHQ domain of CBP has not been attributed to promote survival in any other neurodegenerative disorders.Conclusions/SignificanceWe have identified CBP as a genetic modifier of Aβ42 mediated neurodegeneration. Furthermore, we have identified BHQ domain of CBP is responsible for its neuroprotective function. These studies may have significant bearing on our understanding of genetic basis of AD.

Herein, a stimulus-responsive theranostic nanosystem comprising gold nanorattles (AuNRTs), having a solid octahedron core and thin porous cubic shell, encapsulated within chitosan nanocarriers (CS-AuNRT) has been reported. Due to the plasmonic AuNRTs, CS-AuNRT demonstrated unique features of near infrared (NIR) absorbance and accessible intrinsic electromagnetic “hot spots” arising due to coupling of inner solid core and outer porous shell. These properties enabled CS-AuNRTs to be used for NIR-responsive drug delivery, photothermal therapy, and surface enhanced Raman scattering (SERS) based bioimaging. Following loading of chemotherapeutic drug doxorubicin (DOX) within AuNRTs along with a phase changing material (PCM), application of NIR irradiation resulted in photothermal melting of the PCM and simultaneous payload release in the surrounding medium. Although being nontoxic themselves, CS-AuNRTs with or without loaded DOX could mount significant cell death in breast cancer cell line (MCF-7) in the presence of NIR light as external stimulus. The oxidative stress generated by DOX-loaded and empty CS-AuNRTs upon NIR irradiation were confirmed by flow-cytometric determination of intracellular reactive oxygen species (ROS). Further, the ROS-led induction of apoptosis in treated MCF-7 cells was established from characteristic nuclear fragmentation, morphological changes and membrane blebbing as observed through confocal fluorescence and scanning electron microscopy. Thus, with NIR responsive chemo-photothermal therapy and SERS based bioimaging, the present nanocarrier system holds potential for cancer theranostics.