Buoyancy-Driven Micro/-Nanomotors: From Fundamentals to Applications.

The progression of self-powered micro/-nanomotors (MNMs) has rapidly evolved over the past few decades, showing applications in various fields such as nanotechnology, biomedical engineering, microfluidics, environmental science, and energy harvesting. Miniaturized MNMs transduce chemical/biochemical energies into mechanical motion for navigating through complex fluidic environments with directional control via external forces fields such as magnetic, photonic, and electric stimuli. Among various propulsion mechanisms, buoyancy-driven MNMs have received noteworthy recognition due to their simplicity, efficiency, and versatility. Buoyancy force-driven motors harness the principles of density variation-mediated force to overcome fluidic resistance to navigate through complex environments. Restricting the propulsion in one direction helps to control directional movement, making it more efficient in isotropic solutions. The changes in pH, ionic strength, chemical concentration, solute gradients, or the presence of specific molecules can influence the motion of buoyancy-driven MNMs as evidenced by earlier reports. This review aims to provide a fundamental and detailed analysis of the current state-of-the-art in buoyancy-driven MNMs, aiming to inspire further research and innovation in this promising field.

pH-Responsive and Reversible A-Motif-Based DNA Hydrogel: Synthesis and Biosensing Application.

Functional DNA hydrogels with various motifs and functional groups require perfect sequence design to avoid cross-bonding interference with themselves or other structural sequences. This work reports an A-motif functional DNA hydrogel that does not require any sequence design. A-motif DNA is a noncanonical parallel DNA duplex structure containing homopolymeric deoxyadenosines (poly-dA) strands that undergo conformation changes from single strands at neutral pH to a parallel duplex DNA helix at acidic pH. Despite this and other advantages over other DNA motifs like no cross-bonding interference with other structural sequences, the A-motif has not been explored much. We successfully synthesized a DNA hydrogel by using an A-motif as a reversible handle to polymerize a DNA three-way junction. The A-motif hydrogel was initially characterized by electrophoretic mobility shift assay, and dynamic light scattering, which showed the formation of higher-order structures. Further, we used imaging techniques like atomic force microscopy and scanning electron microscope to validating its hydrogel like highly branched morphology. pH-induced conformation transformation from monomers to gel is quick and reversible, and was analysed for multiple acid-base cycles. The sol-to-gel transitions and gelation properties were further examined in rheological studies. The use of the A-motif hydrogel in the visual detection of pathogenic target nucleic acid sequence was demonstrated for the first time in a capillary assay. Moreover, pH-induced hydrogel formation was observed in situ as a layer over the mammalian cells. The proposed A-motif DNA scaffold has enormous potential in designing stimuli-responsive nanostructures that can be used for many biological applications.

Carrollian Origins of Bjorken Flow.

Bjorken flow is among the simplest models of fluids moving near the speed of light (c), while Carroll symmetry arises as a contraction of Poincaré group when c→0. We show that Bjorken flow and its phenomenological approximations are completely captured by Carrollian fluids. Carrollian symmetries arise on generic null surfaces, and a fluid moving at c is restricted to such a surface, thereby naturally inheriting the symmetries. Carrollian hydrodynamics is, thus, not exotic, but rather ubiquitous, and provides a concrete framework for fluids moving at or near the speed of light.

Solution combustion synthesis, characterization, magnetic, and dielectric properties of CoFe2O4 and Co0.5M0.5Fe2O4 (M = Mn, Ni, and Zn).

Nanocrystalline CoFe2O4 and Co0.5M0.5Fe2O4 (M = Mn, Ni, and Zn) ferrites were prepared by the solution combustion method using oxalyl dihydrazide as a fuel. These materials were characterized by several physicochemical techniques. X-ray diffraction (XRD) patterns indicate the cubic spinel structure of these ferrites. Field emission scanning electron microscopy (FESEM) images demonstrate the microporous nature of the materials because of the large amount of gas production during their synthesis. High resolution transmission electron microscopy (HRTEM) images show lattice fringes corresponding to the {220} and {311} planes of the spinel structure. Fourier transform infrared (FTIR) spectra exhibit absorption bands around the 500-600 cm-1 wavenumber region which are related to metal-oxygen bonds with tetrahedral coordination. Symmetric and asymmetric stretching and symmetric bending modes associated with tetrahedral and octahedral cations present in the spinel structures have been assessed by Raman spectroscopy. X-ray photoelectron spectroscopy (XPS) studies demonstrate the presence of Co2+, Mn2+, Ni2+, Zn2+, and Fe3+ in tetrahedral and octahedral coordinations in these ferrites. Co0.5Zn0.5Fe2O4 is observed to show the highest saturation magnetization among all these materials. The dielectric measurements reveal that the dielectric constant and loss values decrease with an increase in frequency and the ac conductivity increases at higher frequencies due to mobilization of the charge carriers.

Toxicity Concerns of Therapeutic Nanomaterials.

In the modern era, research on the synthesis of nanoparticles (NPs) has been growing exponentially. Due to their small size together with extra-ordinary physico-chemical properties, a variety of NPs i.e., metallic, carbon-based, fluorescent, and polymer-based have been exploited in different fields such as tissue engineering, drug delivery, and various other therapeutic applications. Instead of multi-disciplinary applications of NPs, research dealing with the toxicity concerns and influence of such materials, on the public health, plants and environment is still in its infancy. NPs can cause damage at the cellular, sub-cellular, molecular and protein levels owing to their extremely small size, large surface area to volume ratio, shape, and surface functionality. The present review is aimed to provide wide-ranging information related to NPs toxicology, the mechanisms of action, routes of their entry into the body and probable impacts on human health. Understanding of NPs entry routes into the body entails further research so as to update policymakers and regulatory bodies about the toxicity concerns associated with these nanomaterials. Proper characterization of NPs, factors affecting uptake and toxicity of NPs, as well as an understanding of processes when NPs come in contact with living beings, is critical to estimate the possible hazards.

Investigation of modal-interference-induced fiber optic refractive index sensor: markedly enhanced sensitivity realized by shining an optical vortex beam.

A highly sensitive multimode-interference-based refractive index sensor is reported here by shining an optical vortex beam. The sensor probe is formed by splicing a length of no-core fiber in between two air-core vortex fibers. The coupling characteristics of various modes inside the sensor and their effect on sensing properties are numerically analyzed. Simulation results show that the sensing scheme proffers a maximum sensing resolution of 7.59×10-6 and 4.18×10-6 RIU for no-core fiber length of 29.40 and 44.60 mm, respectively. Because of its high sensitivity, the study has potential applications in the chemical and biological sensing fields.

Analyzing bacterial detection and transport using redox impact electrochemistry.

Understanding bacterial transport dynamics, particularly at the single-particle level, is crucial across diverse fields from environmental science to biomedical research. In recent times, the emerging impact electrochemistry method offers a transformative approach for detection of bacteria at the single-particle level. The method employs the principle of single-entity electrochemistry to scrutinize electrochemical processes during interaction with the working electrode. In this study, we utilized redox impact electrochemistry to detect bacteria and analyze their transport processes towards the working electrode. Stochastic detection using redox reactions at the ultramicroelectrode enabled the detection of individual bacteria, with collision resulting in a current spike signal due to charge transfer. Notably, the detection of bacteria was demonstrated at an exceptionally low concentration (100 CFU/mL), with recorded current spikes reaching approximately 8.1 nA. Analysis of integrated areas under these spikes unveiled a diverse distribution of charge transfer at the ultramicroelectrode during redox reactions, implying variations in bacterial sizes, collision positions on the electrode surface, and redox activity among bacteria. Remarkably, the average charge transfer per bacterium between E. coli and the electrode was found to be (244 ± 24) pC, underscoring the intrinsic redox activity of the bacteria, equivalent to (2.52 ± 0.25) × 10-15 mol. Additionally, our investigation explored the effects of cell transport mechanisms, including diffusion, migration, convection, and settlement on stochastic interactions of the bacteria at the ultramicroelectrode. Through the collision frequency calculations, we found that migration is the primary factor shaping bacterial transport, with gravitational cell settlement also exerting a significant influence.

Transferrin Immobilized Graphene Oxide Nanocomposite for Targeted Cancer Chemodynamic Therapy via Increasing Intracellular Labile Fe2+ Concentration.

Recently, different alternative regulated cell death (RCD) pathways, viz., necroptosis, pyroptosis, ferroptosis, cuproptosis etc., have been explored as important targets for the development of cancer medications in recent years, as these can change the immunogenicity of the tumor microenvironment (TME) and will finally lead to the inhibition of cancer progression and metastasis. Here, we report the development of transferrin immobilized graphene oxide (Tfn@GOAPTES) nanocomposite as a therapeutic strategy toward cancer cell killing. The electrostatic immobilization of Tfn on the GOAPTES surface was confirmed by different spectroscopy and microscopy techniques. The Tfn immobilization was found to be ∼74 ± 4%, whereas the stability of the protein on the GO surface suggested a robust nature of the nanocomposite. The MTT assay suggested that Tfn@GOAPTES exhibited cytotoxicity toward HeLa cells via increased lipid peroxidation and DNA damage. Western blot studies resulted in decreased expression of acetylation on lysine 40 of α-tubulin and increased expression of LC3a/b for Tfn@GOAPTES treated HeLa cells, suggesting autophagy to be the main cause of the cell death mechanism. Overall, we predict that the present approach can be used as a therapeutic strategy for cancer cell killing via selective induction of a high concentration of intracellular iron.

Diosgenin loaded cellulose nanoonion impedes different stages of protein aggregation induced cell death via alleviating mitochondrial dysfunction and upregulation of autophagy.

Protein aggregation is a multifaceted phenomenon prevalent in the progression of neurodegenerative diseases, yielding aggregates of diverse sizes. Recently, increased attention has been directed towards early protein aggregates due to their pronounced toxicity, largely stemming from inflammation mediated by reactive oxygen species (ROS). This study advocates for a therapeutic approach focusing on inflammation control rather than mere ROS inhibition in the context of neurodegenerative disorders. Here, we introduced Camellia sinensis cellulose nanoonion (CS-CNO) as an innovative, biocompatible nanocarrier for encapsulating the phytosteroid diosgenin (DGN@CS-CNO). The resulting nano-assembly, manifesting as spherical entities with dimensions averaging ~180-220 nm, exhibits a remarkable capacity for the gradual and sustained release of approximately 39-44 % of DGN over a 60-hour time frame. DGN@CS-CNO displays a striking ability to inhibit or disassemble various phases of hen egg white lysozyme (HEWL) protein aggregates, including the early (HEWLEA) and late (HEWLLA) stages. In vitro experiments employing HEK293 cells underscore the potential of DGN@CS-CNO in mitigating cell death provoked by protein aggregation. This effect is achieved by ameliorating ROS-mediated inflammation and countering mitochondrial dysfunction, as evidenced by alterations in TNFα, TLR4, and MT-CO1 protein expression. Western blot analyses reveal that the gradual and sustained release of DGN from DGN@CS-CNO induces autophagy, a pivotal process in dismantling intracellular amyloid deposits. In summary, this study not only illuminates a path forward but also presents a compelling case for the utilization of phytosteroid as a formidable strategy against neuroinflammation incited by protein aggregation.

Factors associated with improvement in utilization of cardiac resynchronization therapy in eligible heart failure patients: findings from IMPROVE HF.

BACKGROUND: There is a well-recognized gap between the number of patients in whom cardiac resynchronization therapy (CRT) is indicated based on current guidelines and its actual utilization. In the Registry to Improve the Use of Evidence-Based Heart Failure Therapies in the Outpatient Setting (IMPROVE HF) study, there was a significant increase in the use of CRT at 24 months in patients with heart failure (HF) in comparison to baseline. This study evaluated patient, physician, and practice factors associated with this increase in CRT utilization. METHODS: Patients with reduced left ventricular ejection fraction and chronic HF who met the eligibility criteria for CRT at baseline and 24 months were analyzed. Multivariate analyses using patient, physician, and practice characteristics were performed to evaluate factors associated with increased CRT utilization at 24 months. RESULTS: There were 440 patients eligible for CRT both at baseline and 24 months, with 217 (49.3%) treated at baseline and 374 (85%) treated at 24 months, leading to an absolute increase in use of CRT of 35.7%, P < 0.001. Although serum sodium and the absence of rales had modest associations, none of the patient, physician, or practice characteristics had any significant association with the extent of increase in CRT utilization. There was a significant reduction in the variation of CRT utilization across practice sites after the implementation of the performance improvement initiative. CONCLUSIONS: The performance improvement initiative in IMPROVE HF was the most important factor associated with an increase in guideline-recommended CRT utilization. This improvement in CRT utilization and reduced practice variability was found across a variety of cardiology and multispecialty practice sites.

Bacteria-derived topologies of Cu2O nanozymes exert a variable antibacterial effect.

The ability of bacteria to facilitate fabrication of nanomaterials has been adapted towards bacterial sensing applications. In this work, we fabricate spherical, cubic and truncated octahedron topologies of Cu2O nanoparticles via E. coli-facilitated redox reaction in an electrochemical setup. The Cu2O nanoparticles exhibit cytochrome c oxidase-like activity with the spherical topology displaying higher catalytic rate compared to the other geometries. The topology-dependent catalytic behavior of Cu2O nanoparticles has not been reported previously. The Cu2O nanozymes also display E. coli killing activity in a topology-correlated manner. The E. coli mediated redox reaction in an electrochemical setup is being reported for the first time for synthesis of different topologies of Cu2O which also exert a variable antibacterial effect.

Carbon nanosphere based bifunctional oxidoreductase nano-catalytic agent to mitigate hypoxia in cancer cells.

Developing metal-free carbon nanozyme for tumor hypoxia is difficult. In biomedical applications, especially in the case of biomolecular detection, extensive research has been done on nanozymes with enzyme-mimicking catalytic activity. However, there are considerably fewer investigations on targeted nano-catalytic tumor therapy. Nano catalytic medicine-enabled chemotherapy is a safe and promising treatment strategy that involves the conversion of excess H2O2 into O2 in a tumor environment. Here we have synthesized carbon nanosphere (CNS) using the Camellia sinensis plant (CS-CNS). Further surface functionalization was achieved via nitrilotriacetic acid conjugation (NTA@CS-CNS). A stability study of synthesized nanozyme in the presence of various cations, anions, and 5 different pH range suggested the robustness of carbon based nanoassembly. The catalytic in vitro study shows that NTA@CS-CNS mimics peroxidase and catalase using TMB and H2O2 as substrates. NTA@CS-CNS showed Km and Vmax values of ~ 193.2 µM and 0.43 µM/s, ~ 413 µM and 1.42 µM/s, and ~ 378 µM and 1.63 µM/s, respectively when H2O2 and TMB was used for CAT and POD activity. Results showed that NTA@CS-CNS in combination with SFN and laser irradiation reduces hypoxia. Hence, our study could pave the path for the development of different non-toxic nano catalytic therapy for tumors in cancerous cells.

A review on nanotechnological perspective of "the amyloid cascade hypothesis" for neurodegenerative diseases.

Neurodegenerative diseases (NDs) are characterized by progressive degeneration of neurons which deteriorates the brain functions. An early detection of the onset of NDs is utmost important, as it will provide the fast treatment strategies to prevent further progression of the disease. Conventionally, accurate diagnosis of the brain related disorders is difficult in their early phase. To solve this problem, nanotechnology based neurofunctional imaging and biomarker detection techniques have been developed which allows high specificity and sensitivity towards screening and diagnosis of NDs. Another challenge to treat the brain related disorders is to overcome the complex integrity of blood-brain-barrier (BBB) for the delivery of theranostic agents. Fortunately, utilization of nanomaterials has been pursued as promising strategy to address this challenge. Herein, we critically highlighted the recent improvements in the field of neurodiagnostic and therapeutic approaches involving innovative strategies for diagnosis, and inhibition of protein aggregates. We have provided particular emphasis on the use of nanotechnology which can push forward the blooming research growth in this field to win the battle against devastating NDs.

Functional fluorescent nanomaterials for the detection, diagnosis and control of bacterial infection and biofilm formation: Insight towards mechanistic aspects and advanced applications.

Infectious diseases resulting from the high pathogenic potential of several bacteria possesses a major threat to human health and safety. Traditional methods used for screening of these microorganisms face major issues with respect to detection time, selectivity and specificity which may delay treatment for critically ill patients past the optimal time. Thus, a convincing and essential need exists to upgrade the existing methodologies for the fast detection of bacteria. In this context, increasing number of newly emerging nanomaterials (NMs) have been discovered for their effective use and applications in the area of diagnosis in bacterial infections. Recently, functional fluorescent nanomaterials (FNMs) are extensively explored in the field of biomedical research, particularly in developing new diagnostic tools, nanosensors, specific imaging modalities and targeted drug delivery systems for bacterial infection. It is interesting to note that organic fluorophores and fluorescent proteins have played vital role for imaging and sensing technologies for long, however, off lately fluorescent nanomaterials are increasingly replacing these due to the latter's unprecedented fluorescence brightness, stability in the biological environment, high quantum yield along with high sensitivity due to enhanced surface property etc. Again, taking advantage of their photo-excitation property, these can also be used for either photothermal and photodynamic therapy to eradicate bacterial infection and biofilm formation. Here, in this review, we have paid particular attention on summarizing literature reports on FNMs which includes studies detailing fluorescence-based bacterial detection methodologies, antibacterial and antibiofilm applications of the same. It is expected that the present review will attract the attention of the researchers working in this field to develop new engineered FNMs for the comprehensive diagnosis and treatment of bacterial infection and biofilm formation.

Electrochemical Energy Harvesting Using Microbial Active Matter.

With the continuous growth in world population and economy, the global energy demand is increasing rapidly. Given that non-renewable energy sources will eventually deplete, there is increasing need for clean, alternative renewable energy sources, which will be inexpensive and involve minimum risk of environmental pollution. In this paper, harnessing the activity of cupric reductase NDH-2 enzyme present in Escherichia coli bacterial cells, we demonstrate a simple and efficient energy harvesting strategy within an electrochemical chamber without the requirement of any external fuels or force fields. The transduction of energy has been demonstrated with various strains of E. coli, indicating that this strategy could, in principle, be applicable for other microbial catalytic systems. We offer a simple mechanism of the energy transduction process considering the bacterial enzyme-mediated redox reaction occurring over the working electrode of the electrochemical cell. Also, the amount of energy generated has been found to be depending on the motility of bacteria within the experimental chamber, suggesting possible opportunities for developing microbial motility-controlled small scale power generators. Finally, we show that the Faradaic electrochemical energy harvested is large enough to power a commercial light emitting diode connected to an amplifier circuit. We expect the present study to generate sufficient interest within soft condensed matter and biophysics communities, and offer useful platforms for controlled energy generation at the small scales.

Correction: Assessing insecticide susceptibility, diagnostic dose and time for the sand fly Phlebotomus argentipes, the vector of visceral leishmaniasis in India, using the CDC bottle bioassay.

[This corrects the article DOI: 10.1371/journal.pntd.0010613.].

Assessing insecticide susceptibility, diagnostic dose and time for the sand fly Phlebotomus argentipes, the vector of visceral leishmaniasis in India, using the CDC bottle bioassay.

Visceral leishmaniasis (VL) is a vector-borne protozoan disease, which can be fatal if left untreated. Synthetic chemical insecticides are very effective tools for controlling of insect vectors, including the sand fly Phlebotomus argentipes, the vector of VL in the Indian subcontinent. However, repeated use of the same insecticide with increasing doses potentially can create high selection pressure and lead to tolerance and resistance development. The objective of this study was to determine the lethal concentrations and assess levels of susceptibility, diagnostic doses and times to death of laboratory-reared P. argentipes to five insecticides that are used worldwide to control vectors. Using the Center for Disease Control and Prevention (CDC) bottle bioassay, 20-30 sand flies were exposed in insecticide- coated 500-ml glass bottles. Flies were then observed for 24 hours and mortality was recorded. Dose-response survival curves were generated for each insecticide using QCal software and lethal concentrations causing 50%, 90% and 95% mortality were determined. A bioassay was also conducted to determine diagnostic doses and diagnostic times by exposing 20-30 flies in each bottle containing set concentrations of insecticide. Mortality was recorded at 10-minute intervals for 120 minutes to generate the survival curve. Phlebotomus argentipes are highly susceptible to alpha-cypermethrin, followed by deltamethrin, malathion, chlorpyrifos, and least susceptible to DDT. Also, the lowest diagnostic doses and diagnostic times were established for alpha-cypermethrin (3µg/ml for 40 minutes) to kill 100% of the flies. The susceptibility data, diagnostic doses and diagnostic times presented here will be useful as baseline reference points for future studies to assess insecticide susceptibility and resistance monitoring of field caught sand flies and to assist in surveillance as VL elimination is achieved in the region.

Risk of colorectal adenomas in women with prior breast cancer.

BACKGROUND AND AIMS: Longer life expectancy in patients with prior breast cancer may increase their risk of developing other primary cancers, including colorectal cancer (CRC). Whether the risk of developing CRC in this patient population is higher in comparison to those with no prior cancer remains unclear. The purpose of this study was to compare the prevalence of colorectal adenomas and any CRC in breast cancer survivors with those who have no history of prior cancer and assess any difference with use of antiestrogen therapy. METHODS: We compared the prevalence of colorectal cancer and adenomas in breast cancer survivors with that of a group of matched controls. Eligible survivors were ≤85 years of age; had initially been diagnosed with stage 0, I, II, or III breast cancer; had completed all cancer treatments with the exception of adjuvant antiestrogen therapy; and had no evidence of recurrence on follow-up. We used the screening colonoscopy database at our institution to identify age-, sex-, and race-matched controls with no history of cancer. RESULTS: We identified 302 study-eligible breast cancer survivors and 302 matched controls. No colorectal cancers were found in either group. Forty-one breast cancer survivors and 30 controls had tubular adenomas; four survivors and three controls had villous adenoma; and eight survivors and ten controls had advanced adenoma. Multivariate regression analysis revealed that adjuvant antiestrogen therapy was not significantly associated with an increased risk of advanced adenoma. CONCLUSIONS: The prevalence of colorectal adenomas in breast cancer survivors and controls was similar. Breast cancer survivors, including those receiving adjuvant antiestrogen therapies may follow the colorectal screening guidelines used for average-risk population.

Radiofrequency Ablation for Prevention of Outflow Tract Obstruction in Percutaneous Mitral Valve-in-Valve Replacement.

Left ventricular outflow tract obstruction (LVOTO) can complicate percutaneous mitral valve replacement and may preclude patients considered high surgical risk from transcatheter therapies. We report a case of mitral valve-in-valve procedure in a patient at high risk for LVOTO. (Level of Difficulty: Advanced.).

Single-walled carbon nanotube conjugated cytochrome c as exogenous nano catalytic medicine to combat intracellular oxidative stress.

Mitochondrial dysfunction has been reported to be one of the main causes of many diseases including cancer, type2 diabetes, neurodegenerative disorders, cardiac ischemia, sepsis, muscular dystrophy, etc. Under in vitro conditions, Cytochrome C (Cyt C) maintains mitochondrial homeostasis and stimulates apoptosis, along with being a key participant in the life-supporting function of ATP synthesis. Hence, the medicinal importance of Cyt C as catalytic defense is immensely important in various mitochondrial disorders. Here, we have developed a nanomaterial via electrostatically conjugating oxidized single-wall carbon nanotube with Cyt C (Cyt C@cSWCNT) for the exogenous delivery of Cyt C. The chemical and morphological characterization of the developed Cyt C@cSWCNT was done using UV-vis, FTIR, XPS, powder XRD, TGA/DSC, TEM, etc. The developed Cyt C@cSWCNT exhibited bifunctional catalase and peroxidase activity with Km (∼ 642.7 µM and 351.6 µM) and Vmax (∼0.33 µM/s and 2.62 µM/s) values, respectively. Also, through this conjugation Cyt C was found to retain its catalytic activity even at 60 °C, excellent catalytic recyclability (at least up to 3 times), and wider pH activity (pH = 3 to 9). Cyt C@cSWCNT was found to promote intracellular ROS quenching and maintain mitochondrial membrane potential and cellular membrane integrity via Na+/K+ ion homeostasis during the H2O2 stress. Overall the present strategy provides an alternative approach for the exogenous delivery of Cyt C which can be used as nano catalytic medicine.