Model-Agnostic Binary Patch Grouping for Bone Marrow Whole Slide Image Representation.

Histopathology is the reference standard for pathology diagnosis, and has evolved with the digitization of glass slides [ie, whole slide images (WSIs)]. While trained histopathologists are able to diagnose diseases by examining WSIs visually, this process is time consuming and prone to variability. To address these issues, artificial intelligence models are being developed to generate slide-level representations of WSIs, summarizing the entire slide as a single vector. This enables various computational pathology applications, including interslide search, multimodal training, and slide-level classification. Achieving expressive and robust slide-level representations hinges on patch feature extraction and aggregation steps. This study proposed an additional binary patch grouping (BPG) step, a plugin that can be integrated into various slide-level representation pipelines, to enhance the quality of slide-level representation in bone marrow histopathology. BPG excludes patches with less clinical relevance through minimal interaction with the pathologist; a one-time human intervention for the entire process. This study further investigated domain-general versus domain-specific feature extraction models based on convolution and attention and examined two different feature aggregation methods, with and without BPG, showing BPG's generalizability. The results showed that using BPG boosts the performance of WSI retrieval (mean average precision at 10) by 4% and improves WSI classification (weighted-F1) by 5% compared to not using BPG. Additionally, domain-general large models and parameterized pooling produced the best-quality slide-level representations.

Measurement of microRNA-106b as a gastric cancer biomarker based on Zn-BTC MOF label-free genosensor.

Due to the late detection of stomach cancer, this cancer usually causes high mortality. The development of an electrochemical genosensor to measure microRNA 106b (miR-106b), as a gastric cancer biomarker, is the aim of this effort. In this regard, first, 1,3,5-benzenetricarboxylate (BTC) metal-organic frameworks (Zn-BTC MOF) were self-assembled on the glassy carbon electrode and then the probe (ssDNA) was immobilized on it. The morphology Zn-BTC MOF was characterized by SEM, FT-IR, Raman and X-Ray techniques. Zn-BTC MOF as a biosensor substrate has strong interaction with ssDNA. Quantitative measurement of miR-106b was performed by electrochemical impedance spectroscopy (EIS). To perform this measurement, the difference of the charge transfer resistances (ΔRct) of Nyquist plots of the ssDNA probe modified electrode before and after hybridization with miR-106b was obtained and used as an analytical signal. Using the suggested genosensor, it is possible to measure miR-106b in the concentration range of 1.0 fM to 1.0 µM with a detection limit of 0.65 fM under optimal conditions. Moreover, at the genosensor surface, miR-106b can be detected from a non-complementary and a single base mismatch sequence. Also, the genosensor was used to assess miR-106b in a human serum sample and obtained satisfactory results.

Effect of Virgin Coconut Oil Supplementation on Cognition of Individuals with Mild-to-Moderate Alzheimer's Disease in Sri Lanka (VCO-AD Study): A Randomized Placebo-Controlled Trial.

BACKGROUND: Virgin coconut oil (VCO) is a potential therapeutic approach to improve cognition in Alzheimer's disease (AD) due to its properties as a ketogenic agent and antioxidative characteristics. OBJECTIVE: This study aimed to investigate the effect of VCO on cognition in people with AD and to determine the impact of apolipoprotein E (APOE) ɛ4 genotype on cognitive outcomes. METHODS: Participants of this double-blind placebo-controlled trial (SLCTR/2015/018, 15.09.2015) were 120 Sri Lankan individuals with mild-to-moderate AD (MMSE = 15-25), aged > 65 years, and they were randomly allocated to treatment or control groups. The treatment group was given 30 mL/day of VCO orally and the control group, received similar amount of canola oil, for 24 weeks. The Mini-Mental Sate Examination (MMSE) and Clock drawing test were performed to assess cognition at baseline and at the end of the intervention. Blood samples were collected and analyzed for lipid profile and glycated hemoglobin (HbA1 C) levels.∥Results:There were no significant difference in cognitive scores, lipid profile, and HbA1 C levels between VCO and control groups post-intervention. The MMSE scores, however, improved among APOE ɛ4 carriers who had VCO, compared to non-carriers (2.37, p = 0.021). APOE ɛ4 status did not influence the cognitive scores in the control group. The attrition rate was 30%.∥Conclusion:Overall, VCO did not improve cognition in individuals with mild-to-moderate AD following a 24-week intervention, compared to canola oil. However, it improved the MMSE scores in APOE ɛ4 carriers. Besides, VCO did not compromise lipid profile and HbA1 C levels and is thus safe to consume.

Interactive Effects of Selenium, Zinc, and Iron on the Uptake of Selenium in Mycelia of the Culinary-Medicinal Winter Mushroom Flammulina velutipes (Agaricomycetes).

The present study for the first time addressed whether the simultaneous presence of selenium, zinc and iron may have effects on the selenium uptake in the mycelia of the winter mushroom (also known as enoki), Flammulina velutipes. Response surface methodology was used to optimize concentrations of selenium, zinc and iron in the range of 0 to 120 mg L-1. The findings showed that application of selenium, zinc and iron (singly, in pairs, or triads) significantly enhanced the selenium accumulation in the mycelia. The highest amount of the selenium accumulation was observed when selenium (60 mg L-1) and zinc (120 mg L-1) were applied into submerged culture media, concurrently, leading to an 85-fold and 88-fold increase in the selenium content of the mycelia compared to that of the mycelia treated with selenium only and untreated mycelia, respectively. In addition, accumulation of selenium into the mycelia had no deteriorative effects on the mycelial biomass. The findings presented in this study may have implications for daily nutrition and industrial bioproduction of mushroom mycelia enriched with selenium.

Antibacterial Activity of Culinary-Medicinal Polypore Mushroom Lentinus tigrinus (Agaricomycetes).

Medicinal mushrooms belonging to Lentinus spp. exhibit significant antibacterial activities, but little attention has been paid to their efficacy against the food-borne pathogen, Bacillus cereus. The present study for the first time quantitatively evaluated the antibacterial activity of different extracts from fruiting bodies of a well-authenticated Iranian native strain of medicinal mushroom, Lentinus tigrinus, against Gram-positive spore-forming bacterium B. cereus. The findings revealed that the acetone extract inhibited the growth of B. cereus at concentrations as low as 31.25 µg/ML, while it had no effect against Escherichia coli and Staphylococcus aureus even at 10,000 µg/ML. The rest of the bacteria were also susceptible to the acetone extract at concentrations greater than 5 mg/ML. Antibacterial activities of the methanol-ethyl acetate extract and the hot water extract were significantly weaker than that of the acetone extract, which contained high amounts of total phenols (5.83 ± 0.08 mg GAE/g, dw), while Fourier transform infrared spectroscopy (FT-IR) confirmed the presence of functional groups, such as hydroxyl, carbonyl, amide, and amine. Further studies by scanning electron microscopy (SEM) confirmed obvious changes in the morphology of B. cereus in response to the acetone extract of L. tigrinus. This study may suggest that L. tigrinus could be a good natural source for isolating and purifying antibacterial compounds against B. cereus.

Management of Migraine-Associated Vestibulocochlear Disorders.

Migraine is a chronic neurological disorder that frequently coexists with different vestibular and cochlear symptoms (sudden hearing loss, tinnitus, otalgia, aural fullness, hyperacusis, dizziness, imbalance, and vertigo) and disorders (recurrent benign positional vertigo, persistent postural perceptual dizziness, mal de debarquement, and Menière's disease). Despite evidence of an epidemiological association and similar pathophysiology between migraine and these vestibulocochlear disorders, patients suffering from migraine-related symptoms are usually underdiagnosed and undertreated. Current migraine treatment options have shown success in treating vestibulocochlear symptoms. Lifestyle and dietary modifications (reducing stress, restful sleep, avoiding migraine dietary triggers, and avoiding starvation and dehydration) and supplements (vitamin B2 and magnesium) offer effective first-line treatments. Treatment with migraine prophylactic medications such as tricyclic antidepressants (e.g., nortriptyline), anticonvulsants (e.g., topiramate), and calcium channel blockers (e.g., verapamil) is implemented when lifestyle and dietary modifications are not sufficient in improving a patient's symptoms. We have included an algorithm that outlines a suggested approach for addressing these symptoms, taking into account our clinical observations. Greater recognition and understanding of migraine and its related vestibular and cochlear symptoms are needed to ensure the appropriate diagnosis and treatment of affected patients.

Meniere's disease is a manifestation of migraine.

PURPOSE OF REVIEW: To discuss the theory that Meniere's disease (MD) is a variation of otologic migraine rather than an isolated inner ear condition. RECENT FINDINGS: In contrast to the approximately 12% of the general population suffering from migraine headaches, 51-60% of patients with MD experience migraine headaches. While pathognomonic for MD, endolymphatic hydrops has also been identified in patients with vestibular migraine. Treatment with the integrative neurosensory rehabilitation approach (diet and lifestyle changes, magnesium and riboflavin supplementation, and when needed, prophylactic medication) to treat the underlying migraine process has been highly effective in patients with MD. SUMMARY: MD can be understood as a manifestation of migraine such that patients with MD can be effectively treated with migraine therapies.

Role of Ommaya Reservoir in Pediatric Hydrocephalus: Experience in Bangladesh Medical College Hospital from 2019-2021.

The goal of this study was to analyze the efficacy of the Ommaya reservoir within all the different types of hydrocephalus in pediatric patients. At the same time, it's safe for repeated aspirations or long-term retention of the reservoir in the body. This retrospective, cross-sectional study was performed from January 2019 to December 2021, 33 consecutive cases of reservoir implantation were taken into the study irrespective of the etiology of hydrocephalus in the Neurosurgery Department of Bangladesh Medical College Hospital, Dhaka, Bangladesh. These were mostly placed along with endoscopic third ventriculostomy and some were placed as an intermediary procedure to combat shunt complications in emaciated infants. Cerebrospinal fluid (CSF) aspiration was done in case of failed endoscopic third ventriculostomy and the frequency of aspiration depended upon the production of cerebrospinal fluid. Acetazolamide was routinely administered in each patient to reduce the frequency of aspiration. Most of the patients required ventriculo-peritoneal (VP) shunt while they had sufficient body weight and few required no surgery. The average age at presentation was 76.88 days. All the neonates and infants had less weight in terms of their age. 42.4% of babies needed aspiration 2 times per week. Among all cases, 9.1% developed reservoir complications. Complications were not related to the number and volume of aspiration or duration of the reservoir in the body. Two (2) patients died after one year of reservoir implantation due to unknown etiology. Out of the 31 survivors, 3 patients did not need any further aspiration and 19 patients needed a ventriculo-peritoneal shunt, but the reservoir was kept in situ for a future emergency. The rest of them is waiting for a definitive shunt procedure. Other findings include low socioeconomic group was more prone to low birth weight and they carried the burden of congenital hydrocephalus and meningomyelocele. Most affected babies had their prenatal period in arsenic-affected areas in Bangladesh. Overall folic acid supplementation was started after the formation of the neural tube irrespective of socioeconomic status. Ommaya reservoir placement along with endoscopic third ventriculostomy plays a vital role in delaying shunt in endoscopic third ventriculostomy failure. It is a 'time buying' procedure until the baby has sufficient weight for successful shunt surgery. It has been found very effective intermediary intervention for managing shunt infection and it also helps revive a channel in shunt obstruction.

Berberine promotes immunological outcomes and decreases neuroinflammation in the experimental model of multiple sclerosis through the expansion of Treg and Th2 cells.

INTRODUCTION: Among the most frequent demyelinating autoimmune disorders of the central nervous system (CNS) is multiple sclerosis. Experimental autoimmune encephalomyelitis (EAE) is used as an animal model of multiple sclerosis. Berberine is an alkaloid found in some medicinal plants with anti-inflammatory effects. METHODS: C57BL/6 female mice were used and divided into three groups: (1) The control group received PBS, (2) the low-dose treatment group received 10 mg/kg of berberine, and (3) The high-dose treatment group received 30 mg/kg of berberine. Myelin Oligodendrocyte Glycoprotein and complete Freund's adjuvant were subcutaneously administered to induce EAE. Mice were given intraperitoneal injections of pertussis toxin on the day of immunization and 2 days later. Histological studies showed low lymphocyte infiltration and demyelination of CNS in the treated groups. RESULTS: The clinical scores of the treatment group with low-dose berberine (T1: 2 ± 0.13) and high-dose berberine (T2: 1.5 ± 0.14) were significantly (p < .001) lower than the control group (CTRL: 4.5 ± 0.13). Treatment groups decreased pro-inflammatory cytokines (IFN-γ, TNF-α, interleukin [IL]-17) (p < .001) as well as increased anti-inflammatory cytokine expression (IL-4, IL-10, IL-27, IL-33, IL-35, TGF-ß) (p < .01) when compared to the CTRL group. Treatment groups with berberine reduced expression of the Th1 and Th17 cytokines and transcription factors (p < .001) and increased expression of transcription factors and Th2 and Treg cytokines (p < .01) in contrast to CTRL group. CONCLUSION: Berberine appears to have a protective effect on disease development and alleviating disease status in EAE, which appears to be due to the cell expansion and function of Treg and Th2 cells in addition to berberine's anti-inflammatory properties.

Medium-chain fatty acids for the prevention or treatment of Alzheimer's disease: a systematic review and meta-analysis.

CONTEXT: In preclinical Alzheimer's disease (AD), the brain gradually becomes insulin resistant. As a result, brain glucose utilization is compromised, causing a cellular energy deficit that leads to the accumulation of free radicals, which increases inflammation and damages neurons. When glucose utilization is impaired, ketone bodies offer an alternative energy source. Ketone bodies are synthesized from fats, obtained from either the diet or adipose tissue. Dietary medium-chain fatty acids (MCFAs), which are preferentially metabolized into ketone bodies, have the potential to supply the insulin-resistant brain with energy. OBJECTIVE: This systematic review and meta-analysis aims to review the effect of MCFA supplements on circulating ketone bodies and cognition in individuals with subjective cognitive decline, mild cognitive impairment, and AD. DATA SOURCES: A comprehensive search of electronic databases was performed on August 12, 2019, to retrieve all publications meeting the inclusion criteria. Alerts were then set to identify any publications after the search date up until January 31, 2021. DATA EXTRACTION: Data were extracted by 2 authors and assessed by a third. In total, 410 publications were identified, of which 16 (n = 17 studies) met the inclusion criteria. DATA ANALYSIS: All studies assessing change in levels of blood ketone bodies due to MCFA supplementation (n = 12) reported a significant increase. Cognition outcomes (measured in 13 studies), however, varied, ranging from no improvement (n = 4 studies) to improvement (n = 8 studies) or improvement only in apolipoprotein E allele 4 (APOE ε4) noncarriers (n = 2 studies). One study reported an increase in regional cerebral blood flow in APOE ε4 noncarriers and another reported an increase in energy metabolism in the brain. CONCLUSION: MCFA supplementation increases circulating ketone body levels, resulting in increased brain energy metabolism. Further research is required to determine whether this MCFA-mediated increase in brain energy metabolism improves cognition. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration number CRD42019146967.

The effect of dietary coenzyme Q10 supplementation on egg quality and liver histopathology of layer quails under cadmium challenge.

The demand for quail eggs has been increased over the last decade due to its beneficial nutritional quality characteristics; however, different nutritional and environmental stressors adversely impact the quality of the produced eggs. This study was conducted to investigate whether dietary supplementation of coenzyme Q10 (CoQ10) could mitigate the negative impact of cadmium (Cd) administration on egg quality and liver histopathology. A total of 162 six-week-old laying Japanese quail (Coturnix japonica) were randomly allotted into three experimental groups. Treatments were as follows: (1) negative control (NC): feeding basal diet; (2) positive control (PC): feeding basal diet and Cd administration; and (3) CdQ10: feeding basal diet supplemented with CoQ10 (900 mg/kg diet) and Cd administration. Cadmium (10 mg/kg BW) was subcutaneously administrated at 10 and 11 weeks of age (woa). Feed conversion ratio (FCR), egg production, egg mass, mortality rate, Cd residue in egg, liver histopathology, and some internal and external egg quality indices were evaluated. Administration of Cd increased FCR in the PC group, but supplementation of CoQ10 partially ameliorated the impact of Cd on FCR (p < 0.05). Cadmium administration decreased both egg production and egg mass; however, CoQ10 supplementation partially mitigated these adverse effects of Cd injection in the CdQ10 compared to the PC group (p < 0.05). Cadmium decreased eggshell thickness and Haugh unit in PC quail compared to both NC and CdQ10 quail (p < 0.05). Moreover, egg yolk colour intensity was enhanced by CoQ10, where a* and b* indices were higher in CdQ10 compared to PC (p < 0.05). In conclusion, the current results demonstrate the beneficial effects of dietary CoQ10 supplementation on liver histopathology and some egg quality indices of Cd-challenged quail.

Effects of Nanosilver and Heat Treatment on the Pull-Off Strength of Sealer-Clear Finish in Solid Wood Species.

Pull-off strength is an important property of solid wood, influencing the quality of paints and finishes in the modern furniture industry, as well as in historical furniture and for preservation and restoration of heritage objects. The thermal modification and heat treatment of solid wood have been the most used commercial wood modification techniques over the past decades globally. The effects of heat treatment at two mild temperatures (145 and 185 °C) on the pull-off strength of three common solid wood species, i.e., common beech (Fagus sylvatica L.), black poplar (Populus nigra L.), and silver fir (Abies alba Mill.), were studied in the present research work. The specimens were coated with an unpigmented sealer-clear finish based on an organic solvent. The results demonstrated a positive correlation between the density and pull-off strength in the solid wood species. Heat treatment at 145 °C resulted in an increase in the pull-off strength in all three species, due to the formation of new bonds in the cell-wall polymers. Thermal degradation of the polymers at 185 °C weakened the positive effect of the formation of new bonds, resulting in a largely unchanged pull-off strength in comparison with the control specimens. Impregnation with a silver nano-suspension decreased the pull-off strength in beech specimens. It was concluded that density is the decisive factor in determining the pull-off strength, having a significant positive correlation (R-squared value of 0.89). Heat treatment at lower temperatures is recommended, to increase pull-off strength. Higher temperatures can have a decreasing effect on pull-off strength, due to the thermal degradation of cell-wall polymers.

Migrainous Vertigo, Tinnitus, and Ear Symptoms and Alternatives.

Migraine headaches frequently coexist with vestibular symptoms such as vertigo, motion sickness, and gait instability. Migraine-related vasospasm can also damage the inner ear, which results in symptoms such as sudden sensorineural hearing loss and resultant tinnitus. The pathophysiology of these symptoms is not yet fully understood, and despite their prevalence, there is no universally approved management. This review summarizes the data on complementary and integrative medicine in treating patients with migrainous ear disorders.

Selective Facial Muscle Activation with Acute and Chronic Multichannel Cuff Electrode Implantation in a Feline Model.

OBJECTIVES: Facial paralysis is a debilitating condition with substantial functional and psychological consequences. This feline-model study evaluates whether facial muscles can be selectively activated in acute and chronic implantation of 16-channel multichannel cuff electrodes (MCE). METHODS: Two cats underwent acute terminal MCE implantation experiments, 2 underwent chronic MCE implantation in uninjured facial nerves (FN) and tested for 6 months, and 2 underwent chronic MCE implantation experiments after FN transection injury and tested for 3 months. The MCE were wrapped around the main trunk of the skeletonized FN, and data collection consisted of EMG thresholds, amplitudes, and selectivity of muscle activation. RESULTS: In acute experimentation, activation of specific channels (ie, channels 1-3 and 6-8) resulted in selective activation of orbicularis oculi, whereas activation of other channels (ie, channels 4, 5, or 8) led to selective activation of levator auris longus with higher EMG amplitudes. MCE implantation yielded stable and selective facial muscle activation EMG thresholds and amplitudes up to a 5-month period. Modest selective muscle activation was furthermore obtained after a complete transection-reapproximating nerve injury after a 3-month recovery period and implantation reoperation. Chronic implantation of MCE did not lead to fibrosis on histology. Field steering was achieved to activate distinct facial muscles by sending simultaneous subthreshold currents to multiple channels, thus theoretically protecting against nerve damage from chronic electrical stimulation. CONCLUSION: Our proof-of-concept results show the ability of an MCE, supplemented with field steering, to provide a degree of selective facial muscle stimulation in a feline model, even following nerve regeneration after FN injury. LEVEL OF EVIDENCE: N/A.

Femtomolar determination of an ovarian cancer biomarker (miR-200a) in blood plasma using a label free electrochemical biosensor based on L-cysteine functionalized ZnS quantum dots.

In the present study, a label-free electrochemical genosensor was designed based on ZnS quantum dots functionalized with l-cysteine (Cys-ZnS-QDs) to detect miR-200a, as a special ovarian cancer biomarker. The Cys-ZnS-QD genosensor was characterized by transmission electron microscopy (TEM), UV-Vis absorption and fluorescence methods. Cys-ZnS-QDs are electrodeposited on the glassy carbon electrode surface and act as a suitable substrate for immobilization of the DNA probe. The effective parameters in the preparation of the genosensor are optimized to improve its analytical performance. The analytical performance of the genosensor has been investigated using electrochemical impedance spectroscopy. Under optimal conditions, the linear range and the detection limit of miR-200a were found to be 1.0 × 10-14 to 1.0 × 10-6 M and 8.4 fM. In addition, the genosensor is used to detect the target complementary miRNA strand from a single-base mismatch miRNA strand. Finally, this label-free electrochemical biosensor was used to detect miR-200a in human plasma without using any amplification method.

Improvement and Characterization of Naturally Occurring Folate Compounds in Fruiting Bodies of Culinary-Medicinal Winter Mushroom, Flammulina velutipes (Agaricomycetes).

Edible mushrooms are among food sources containing natural folate compounds. However, little is known about how the content of folates in edible mushrooms may be improved. This study aimed to enrich Flammulina velutipes with higher levels of folates and to characterize patterns of the bioconversion of folates in the fruiting bodies. A convenient method was developed to treat a lignocellulosic substrate with synthetic folic acid. Folate compounds in the fruiting bodies grown in folic acid-treated substrates were evaluated relative to those in untreated substrates. Reverse phase high-performance liquid chromatography revealed different patterns of changes in levels of unsubstituted and substituted folates. While there was an approximately 15-fold and 8-fold increase in 5-formyl tetrahydrofolate and 5-methyl tetrahydrofolate, respectively, the most inconsistency was seen in the tetrahydrofolate content. There were also differences in the level of folate derivatives between commercial and native F. velutipes mushrooms. Since F. velutipes mushrooms can be consumed raw, the enriched mushrooms can be used as a dietary source to meet adult requirements for the daily uptake of natural folates.

Adapting Personal Therapies Using a Mobile Application for Tinnitus Rehabilitation: A Preliminary Study.

OBJECTIVES: To develop a smartphone application providing sound therapy and cognitive behavioral therapy (CBT) for treating tinnitus and performing a proof-of-concept pilot study evaluating its potential efficacy. METHODS: An interactive smartphone application available on iOS and Android platforms was developed, which provided an 8-week tinnitus-specific CBT and personalized and frequency-matched sound therapy. Included patients presented to our tertiary clinic between 2017 and 2018, while those waitlisted were regarded as controls. Three surveys were administrated: Tinnitus Handicap Inventory (THI), Generalized Anxiety Disorder 7-item (GAD-7), and Perceived Stress Scale (PSS). RESULTS: A total of 30 patients enrolled in this study consisting of 20 treatment and 10 control patients and mean age was 55.4 ± 11.6 years. Treatment and control patients had similar age, sex, and pre-enrolment GAD and PSS (all P > .05). Baseline THI scores were also similar between treatment and control cohorts (50.1 ± 21.9 vs 62.0 ± 20.7; P = .15). After 8 weeks, though changes in GAD and PSS scores were similar (P > .05), the treatment group reported a significantly greater improvement in THI scores (17.7 ± 15.8 vs 5.3 ± 10.5, P = .04). CONCLUSIONS: This pilot study demonstrated potentially promising efficacy of a smartphone-based CBT and sound therapy platform for treating tinnitus and encourages future randomized controlled trials on this treatment modality.

LED Photo-polymerization, a Novel Strategy for Triggered Release Liposomes.

LED light is used for many medical and cosmetic applications such as phototherapy and skin rejuvenation. Such physical methods can be combined with drug therapy, such as LED-responsive drug delivery system, the subject of present investigation. To perform this investigation, a nanoliposome composed of DPPC, DSPE-PEG2000, and DC8,9PC, was prepared as LED-sensitive systems. Calcein was loaded in the liposomes as a fluorescent probe for drug release studies. Different LED wavelengths (blue, green and red) were used for triggering release of calcein from nanoliposome. Indoor daylight, darkness, and sunlight were applied as controls. Results showed that liposomes do not release their cargo in darkness, but they released it in response to indoor daylight, sunlight and LEDs, with the blue light showing the highest effect. Results also showed that release of calcein was sensitive to wavelength. Our results reveal potential of LED-sensitive liposomes for medical and cosmetic applications and that such system can be combined with phototherapy. Such concomitant therapies can increase medical/cosmetic effects and decrease adverse reactions to phototherapy.

Identification of free fatty acid receptor 2 agonists using virtual screening.

Structure- and ligand-based virtual-screening methods (docking, 2D- and 3D-similarity searching) were analyzed for their effectiveness in virtual screening against FFAR2. To evaluate the performance of these methods, retrospective virtual screening was performed. Statistical quality of the methods was evaluated by BEDROC and RIE. The results revealed that electrostatic similarity search protocol using EON (ET combo) outperformed all other protocols with outstanding enrichment of >95% in top 1% and 2% of the dataset with an AUC of 0.958. Interestingly, the hit lists that are obtained from different virtual-screening methods are generally highly complementary to hits found from electrostatic similarity searching. These results suggest that considering electrostatic similarity searching first increases the chance of identifying more (and more diverse) active compounds from a virtual-screening campaign. Accordingly, prospective virtual screening using electrostatic similarity searching was used to identify novel FFAR2 ligands. The discovered compounds provide new chemical matter starting points for the initiation of a medicinal chemistry campaign.

Graphene/CuO2 Nanoshuttles with Controllable Release of Oxygen Nanobubbles Promoting Interruption of Bacterial Respiration.

An oxygen nanoshuttle based on a reduced graphene oxide/copper peroxide (rGO/CuO2) nanocomposite has been presented to deliver in situ oxygen nanobubbles (O2 NBs) for combating bacterial infections. In the presence of rGO, the solid source of oxygen (i.e., CuO2) was decomposed (in response to environmental conditions such as pH and temperature) into O2 NBs in a more controllable and long-lasting trend (from 60 to 144 h). In a neutral buffer, the O2 NBs experienced growth and collapse evolutions, creating a dynamic micro-nanoenvironment around the nanocomposite. In addition to effective battling against methicillin-resistant Staphylococcus aureus bacteria, the O2 NBs demonstrated superior antibacterial properties on Gram-positive S. aureus to those on Gram-negative Escherichia coli bacteria, especially in the presence of rGO. In fact, the rGO contents could provide synergistic effects through harvesting some respiratory electrons (leading to striking interruption of the bacterial respiratory pathway) in one side and transferring them into the O2 NBs, resulting in nanoscale reactive oxygen species (ROS) generation in another side. Moreover, near-infrared laser irradiation induced more damage to the cell membrane due to the synergistic effects of local heat elevation and catalyzing the release/collapse of NBs imposing mechanical disruptions. Our results show that the O2-containing nanoshuttles can effectively be used as intelligent and controllable anti-infection nanorobots in upcoming graphene-based nanobiomedical applications.