Greater Activity Research Articles

Recognizing ideas generated in a creative task: the roles of the hippocampus and medial prefrontal cortex in facilitating self-generated learning.

Creative idea generation plays an important role in promoting successful memory formation. Yet, its underlying neural correlates remain unclear. We investigated the self-generated learning of creative ideas motivated by the schema-linked interactions between medial prefrontal and medial temporal regions framework. This was achieved by having participants generate ideas in the alternative uses task, self-evaluating their ideas based on novelty and source (i.e. new or old), and then later being tested on the recognition performance of the generated ideas. At the behavioral level, our results indicated superior performances in discriminating novel ideas, highlighting the novelty effect on memory. At the neural level, the regions-of-interest analyses revealed that successful recognition of novel ideas was associated with greater activations in the hippocampus (HPC) and medial prefrontal cortex (mPFC) during ideation. However, only activation in the right HPC was positively related to the successful recognition of novel ideas. Importantly, the weaker the connection between the right HPC and left mPFC, the higher the recognition accuracy of novel ideas. Moreover, activations in the right HPC and left mPFC were both effective predictors of successful recognition of novel ideas. These findings uniquely highlight the role of novelty in promoting self-generated learning of creative ideas.

Visuospatial processing in early brain-based visual impairment is associated with differential recruitment of dorsal and ventral visual streams.

Visuospatial processing impairments are prevalent in individuals with cerebral visual impairment (CVI) and are typically ascribed to "dorsal stream dysfunction" (DSD). However, the contribution of other cortical regions, including early visual cortex (EVC), frontal cortex, or the ventral visual stream, to such impairments remains unknown. Thus, here, we examined fMRI activity in these regions, while individuals with CVI (and neurotypicals) performed a visual search task within a dynamic naturalistic scene. First, behavioral performance was measured with eye tracking. Participants were instructed to search and follow a walking human target. CVI participants took significantly longer to find the target, and their eye gaze patterns were less accurate and less precise. Second, we used the same task in the MRI scanner. Along the dorsal stream, activation was reduced in CVI participants, consistent with the proposed DSD in CVI. Intriguingly, however, visual areas along the ventral stream showed the complete opposite pattern, with greater activation in CVI participants. In contrast, we found no differences in either EVC or frontal cortex between groups. These results suggest that the impaired visuospatial processing abilities in CVI are associated with differential recruitment of the dorsal and ventral visual streams, likely resulting from impaired selective attention.

Abstract PO1-04-14: PLK1 Inhibitor Onvansertib Extends the Response and Overcomes Resistance to Paclitaxel in Palbociclib-resistant HR+ Breast Cancer Patient-derived Xenografts

Abstract Paclitaxel is a first-line chemotherapy for hormone receptor positive (HR+) metastatic breast cancer patients after progression on a combination of endocrine and CDK4/6 inhibitor therapy. Response rate to paclitaxel ranges between 20-40%, and most patients progress due to intrinsic or acquired resistance, leaving them with limited treatment choices. Therapeutic strategies to overcome paclitaxel resistance and extend its clinical benefit are urgently needed. Paclitaxel-resistant tumors have increased expression of polo-like kinase 1 (PLK1), a serine-threonine-protein kinase that regulates mitosis and cell cycle progression. PLK1 has also been shown to mediate resistance to CDK4/6 inhibitor palbociclib in HR+ breast cancer. Onvansertib is an orally bioavailable, highly potent, and selective PLK1 inhibitor in clinical development. Onvansertib exhibited synergy in vitro and showed potent anti-tumor activity in vivo in combination with paclitaxel in ovarian cancer and triple negative breast cancer (TNBC) preclinical models. A phase 1b/2 clinical trial is ongoing to evaluate the safety and efficacy of onvansertib plus paclitaxel in advanced TNBC (NCT05383196). Here we investigated whether the potential of onvansertib and paclitaxel combination could be extended to HR+ breast cancer. Co-treatment with onvansertib and paclitaxel synergistically inhibited the viability of HR+ breast cancer cell lines (MCF-7, T-47D, EFM-19, CAMA-1, ZR-75-1). Compared to the single agents, the combination induced increased apoptosis. The combination was further tested in vivo in patient-derived xenograft (PDX) models. To this end, six HR+ breast cancer PDXs with intrinsic or acquired resistance to palbociclib were established from primary breast tumors (n=1) or metastatic bone biopsies (n=5). The PDX tumors were engrafted subcutaneously in nude mice and the effect of onvansertib (45 mg/kg, oral, 5 days a week) and paclitaxel (15-25mg/kg, IP, once a week) was investigated as monotherapy and in combination. The combination of onvansertib and paclitaxel was tolerated with minimal toxicity and showed enhanced anti-tumor activity compared to either agent alone in all 6 PDX models. Paclitaxel and onvansertib monotherapies had little to no anti-tumor activity in 4 out of 6 PDX models (HBCx124palboR25, HBCx-139 palboR5, HBCx-202 and HBCx-131). Importantly, the combination of onvansertib and paclitaxel induced strong anti-tumor activity in these 4 models. Tumor regression was observed in the 2 PDX models with acquired resistance to palbociclib, HBCx-124palboR25 and HBCx-139palboR5, with 62% (5/8 mice) and 54% (6/11 mice) complete response rates, respectively. The combination showed tumor stasis in HBCx-131 and induced tumor regression in HBCx-202, established from patient resistant to palbociclib. In 2 of the 6 PDXs, paclitaxel exhibited anti-tumor activity, inducing tumor regression in HBCx-137paboR26 and tumor stasis in HBCx-86. In comparison, the combination of onvansertib and paclitaxel had greater activity, inducing tumor regression in both models with a higher rate of complete response than the monotherapy. Complete response rates for paclitaxel versus the combination were 62% and 100% in the HBCx-137palboR26 model and 0% and 67% in the HBCx-86 model. Notably, the antitumor activity of the onvansertib and paclitaxel combination was very durable, showing a robust delay in tumor relapse after stopping therapy. Together, our data strongly support that combining paclitaxel with the PLK1 inhibitor onvansertib extends its benefit and overcomes paclitaxel resistance, and represents a promising therapeutic strategy for HR+ breast cancer patients after progression on a combination of endocrine and CDK4/6 inhibitor therapy. Citation Format: Maya Ridinger, Pierre Painsec, Sreeja Sreekumar, Dalia Gonzalez, Davis Klein, Laura Sourd, Elodie Montaudon, Paul Cottu, Tod Smeal, Elisabetta Marangoni. PLK1 Inhibitor Onvansertib Extends the Response and Overcomes Resistance to Paclitaxel in Palbociclib-resistant HR+ Breast Cancer Patient-derived Xenografts [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-04-14.

Extraction of bioactive compounds from Vitex megapotamica: A study and selection of variables

AbstractFruits are widely used to obtain and study bioactive compounds. Among them, the tarumã (Vitex megapotamica) is still understudied. The extraction of bioactive compounds from the powdered pulp of the ripe fruit of the tarumã was studied from the selection of several variables of the extraction process through the experimental design Plackett–Burman: the pH, the solid:liquid ratio, agitation, and temperature in an extraction time of 3 h. The extracts obtained were evaluated for antioxidant activity by 2,2′‐azino‐bis‐(3‐ethylbenzothiazoline‐6‐sulfonic acid) (ABTS), 2,2‐diphenyl‐1‐picrylhydrazyl (DPPH), and for total phenolic compounds, as well as the presence of flavonoids, anthocyanins, carotenoids, and identification of bioactive compounds was assessed by high‐performance liquid chromatography (HPLC). Using the experimental design, the best extraction condition was defined with a pH of 5, solid:liquid ratio of 1:30, stirring at 100 rpm, with a temperature of 80°C, obtaining 104.21 mg Gallic Acid Equivalent (GAE) 100 g−1 for phenolic compounds total, 742.71 μmol Trolox g−1 for ABTS, and EC50 of 2884.98 mg L−1 for DPPH. From HPLC, the presence of fumaric acid, gallic acid, p‐coumaric acid, and caffeic acid in the extracts was detected. Regarding flavonoids, anthocyanins, and carotenoids, the values obtained were 6.38 mg ECG g−1, 1.67 mg ECG g−1, and 2.89 mg 100 g−1, respectively. The selection of extraction conditions allowed obtaining better levels of bioactive compounds in the powdered pulp of tarumã extract, even with the use of water as a solvent, to avoid the presence of chemical residues in the extract, with antioxidant potential and viability for application in food products.Practical applicationsRecent research suggests a change in perspective regarding the consumption of healthier foods from plants and fruits that have important health properties. In this regard, tarumã (Vitex megapotamica) fruit has been standing out as a potential source of bioactive compounds with significant medicinal properties. The extracts obtained have a significant amount of phenolic compounds, as well as the presence of flavonoids, anthocyanins, and carotenoids, in which all of these have great potential bioactive activities. Thus, a good methodology of extraction and characterization of tarumã extract becomes a crucial part of any food, chemical, or pharmaceutical industry sector. In this regard, the present study with experimental design Plackett–Burman extraction is the way ahead due to high bioactive retention and the cost implications of the process.

Evaluation of the antibacterial and cytotoxic properties of TotalFill and NeoSEALER flo bioceramic sealers

Aim: Evaluation of the antibacterial and cytotoxic properties of TotalFill and NeoSEALER Flo bioceramic sealers compared to AH Plus resin sealer. Materials and Methods: Modified direct contact test was used on three sets of sealers: Freshly mixed sealers, sealers that were 1-day old, and sealers that were 7-day old. After 24 h of incubation, the colony-forming units were digitally counted using Promega Colony Counter after 30 and 60 min of exposure to Enterococcus faecalis. For cytotoxic effect evaluation, 3-(4,5-dimethylthiazol-2-yl)-2-5-diphenyltetrazolium bromide assay was performed at three different time points: 24 h, 48 h, and 120 h after adding the sealer eluates to human gingival fibroblasts, to assess cell viability. Data were analyzed using mixed model analysis of variance followed by post hoc test. Results: TotalFill bioceramic sealer showed the highest bacterial reduction against E. faecalis throughout all intervals. AH Plus showed great antibacterial activity initially which reduced drastically after 7 days. All the sealers showed a reduction in their antibacterial activity with time. TotalFill and NeoSEALER Flo showed very high cell viability in contrast to AH Plus. Conclusion: TotalFill and NeoSEALER Flo demonstrate superior antimicrobial properties against E. faecalis which reduces with time. TotalFill and NeoSEALER Flo demonstrate acceptable biocompatibility against human gingival fibroblasts, which decreased over time.

Circulating Extracellular Vesicles Are Elevated with Prediabetes and Adversely Affect Cerebral Endothelial Nitric Oxide and Endothelin-1 Production

Experimental and clinical studies indicate that a proatherogenic endothelial phenotype develops in the prediabetic, hyperglycemic state providing the platform for accelerated vascular disease with prediabetes and, in turn, type 2 diabetes. Prediabetes (fasting plasma glucose concentrations: 100-125 mg/dL) is associated with an increased risk of stroke. Circulating endothelial cell-derived microvesicles (EMVs) are now recognized as both a biomarker and mediator of vascular health and disease. In fact, EMVs have been shown to be involved in the pathogenesis of cerebrovascular dysfunction leading to increased stroke risk. Circulating EMVs are elevated in adults with prediabetes; whether EMVs associated with the prediabetic state promote endothelial abnormalities known to increase stroke risk is unknown. The experimental aim of this study was to determine the effect of EMVs isolated from adults with prediabetes on brain endothelial cell nitric oxide (NO) and endothelin (ET)-1 production. Circulating EMVs (CD144-PE) were isolated (flow cytometry) from 20 mid-life adults (age:44-69 yr): 10 normoglycemic (NG; 8M/2F; age: 55±2 yr; BMI: 25.7±0.8 kg/m2; fasting plasma glucose: 87±2 mg/dL) and 10 prediabetic (PreD: 8M/2F; 55±2 yr; 27.1±1.5 kg/m2; 107±2 mg/dL). Human cerebral microvascular endothelial cells (hCMECs) were cultured and separately treated with EMVs from each subject. Expression of intracellular proteins of interest was determined by capillary electrophoresis immunoassay. Circulating EMV concentrations were significantly higher (~65%) in PreD vs NG (180±25 vs 110±13 EMV/μL) and significantly associated with plasma glucose concentrations (r=0.48; P=0.03). Phosphorylation is the primary posttranslational modification regulating eNOS enzyme activity. Phosphorylation of Ser1177 confers the greatest activation of eNOS; whereas, phosphorylation at Thr495 reduces eNOS activation. Expression of p-eNOS (Ser1177) was lower (47.6±2.6 vs 58.6±3.5 AU; P=0.02) and p-eNOS (Thr495) higher (82.6±4.4 vs 31.1±2.5 AU; p<0.001) in cells treated with EMVs from PreD vs NG. Concordantly, NO production was ~20% lower (6.0±0.2 vs 7.2±0.4 μmol/L; p<0.05) in cells treated with EMVs from PreD adults. PreD-associated EMVs also significantly increased (~25-70%) the expression of Big ET-1 (804.4±47.7 vs 656.7±30.7 AU) and endothelin converting enzyme (290.0±24.6 vs 169.6±19.0 AU) as well as ET-1 production (30.2±4.3 vs 24.2±2.0 pg/mL) in hCMECs. In summary, EMVs harvested from adults with PreD reduced endothelial nitric oxide synthase (eNOS) activation and NO production and increased ET-1 synthesis and release in brain endothelial cells in vitro. Increased risk and incidence of stroke associated with prediabetes may be mediated by circulating EMVs. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Electromyographic analysis of selected shoulder muscles during shoulder rehabilitation exercises in patients after reverse total shoulder arthroplasty

BackgroundReversed shoulder arthroplasty (RSA) aims to restore function in patients with rotator cuff failure and joint arthropathy. After surgery, patients are routinely referred to a rehabilitation specialist to regain range of motion, strength, and function. A key element in these programs is active exercises. The exercises are often selected based on assumed muscle activity, investigated by electromyography (EMG). In particular, in this patient population, activation of the deltoid and the scapular muscles is the focus of exercise therapy. Currently, most studies investigating muscle activity levels during exercises are performed on healthy individuals. To our knowledge, no study exists analyzing EMG activity during exercises in a population of shoulder arthroplasty patients. Therefore, the study aimed to analyze activity in the shoulder girdle muscles during 6 commonly used rehabilitation exercises 12 weeks after RSA surgery. MethodsForty-four patients (50 shoulders) participated in this cross-sectional study, 12 weeks postoperatively (mean 99.18±12.8 days), aged 68.9±7.75 years. Surface EMG activity was measured in 10 shoulder girdle muscles: the 3 trapezius parts, serratus anterior, the 3 deltoid parts, latissimus dorsi, and 2 pectoralis major parts during 6 exercises, 3 in a closed chain, and 3 open chain elevation exercises. ResultsGravity- minimized exercises (horizontal plane) show low activity for almost all muscles. Vertical closed kinetic chain exercises show an increased activity compared to horizontal plane exercises. Open kinetic chain exercises against gravity showed the greatest activity in Deltoid and Upper trapezius. For the other muscles no consistency in progression was found. ConclusionThis study offers a progression of exercises for patients after reversed shoulder arthroplasty based on increased muscle activity.

Synthesis, characterization, antimicrobial and antioxidant activity of 2- (2′-hydroxyphenyl) -1,3,4-oxadiazolyl-5-amino acid derivatives

The synthesis and biological assessment of 2,5-disubstituted-1,3,4-oxadiazoles derivatives from amino acids as new potential antibacterial and antioxidant agents have been reported. The structures of the new synthesized compounds were characterized based on physicochemical and spectral data UV–Visible, IR, 1HNMR, 13CNMR. All the target compounds were screened for theirin vitroantibacterial activityagainst three Gram-positivebacterial strains,namely Staphylococcus aureus ATCC 25923, Bacillus cereus ATCC 14579, Listeria innocua ATCC 33090, and two Gram-negative bacterial strains,namely Pseudomonas aeruginosa ATCC 27853, Escherichia coli ATCC 25922, andantifungal activityagainst Candida albicans ATCC 10231 in comparison with Amoxicillin, Tetracycline, Gentamicin and Oxacillin. The only compound 1-{(4S)-4-amino-4-[5-(2-hydroxyphenyl)-1,3,4-oxadiazol-2-yl]butyl}guanidine 5e with the amine radical thatshowed excellent results against all bacteria, particularly against L. innocua (IZ = 12 mm), has excellent antifungal activity (IZ = 32 mm). The compounds 2-[5-(1-amino-3-methylbutyl)-1,3,4-oxadiazol-2-yl]phenol 5b and 2-[5-(pyrrolidin-2-yl)-1,3,4-oxadiazol-2-yl]phenol 5j have excellent activities (IZ = 27 and IZ = 28 mm, respectively) against B. cereus and P. aeruginosa. Compounds 2-{5-[(1R)-1-amino-2-sulfanylethyl]-1,3,4-oxadiazol-2-yl}phenol 5c, 2-{5-[(1S)-1-amino-3-(methylsulfanyl)propyl]-1,3,4-oxadiazol-2-yl}phenol 5dwith the sulfur radical, 3--[5-(2-3-amino hydroxyphenyl)-1,3,4-oxadiazol-2-yl]propanamide 5g with the amide radical, 5j with the amino radical, and 4-amino-4-[5-(2-hydroxyphenyl)-1,3,4-oxadiazol-2-yl]butanoic acid 5k gave good results against B. cereus, where 19 mm < IZ < 23 mm. We also found that compound 5j has the greatest activity (IZ = 33 mm) against C. albicans, followed by compounds 5e (IZ = 32 mm) and 5b (IZ = 30 mm). The synthesized compounds were also screened for radical scavenging antioxidant activities by DPPH, FRAP, and TAC assays and found to be good antioxidant agents. According to the IC50 values, all compounds demonstrated good to excellent activity, especially 5b and 2-{5-[1-amino-2-(1H-imidazol-4-yl)ethyl]-1,3,4-oxadiazol-2-yl}phenol 5i for DPPH, 5e and 5i for FRAP and methyl 2-hydroxybenzoate 2,2-{5-[1-amino-2-(1H-indol-3-yl)ethyl]-1,3,4-oxadiazol-2-yl}phenol 5h with the imidazol group and 2-[5-(1,5-diaminopentyl)-1,3,4-oxadiazol-2-yl]phenol 5f with the imidazol group for TAC. All these compounds showed better activity than AA and BHT.

Inhibition of some multidrug-resistant bacteria using prepared essential oil Nanoemulsion formulas and their mode of action

Inhibition of some multidrug-resistant bacteria using prepared essential oil Nanoemulsion formulas and their mode of action

Integrative Genomics and Bioactivity-Guided Isolation of Novel Antimicrobial Compounds from Streptomyces sp. KN37 in Agricultural Applications.

Actinomycetes have long been recognized as an important source of antibacterial natural products. In recent years, actinomycetes in extreme environments have become one of the main research directions. Streptomyces sp. KN37 was isolated from the cold region of Kanas in Xinjiang. It demonstrated potent antimicrobial activity, but the primary active compounds remained unclear. Therefore, we aimed to combine genomics with traditional isolation methods to obtain bioactive compounds from the strain KN37. Whole-genome sequencing and KEGG enrichment analysis indicated that KN37 possesses the potential for synthesizing secondary metabolites, and 41 biosynthetic gene clusters were predicted, some of which showed high similarity to known gene clusters responsible for the biosynthesis of antimicrobial antibiotics. The traditional isolation methods and activity-guided fractionation were employed to isolate and purify seven compounds with strong bioactivity from the fermentation broth of the strain KN37. These compounds were identified as 4-(Diethylamino)salicylaldehyde (1), 4-Nitrosodiphenylamine (2), N-(2,4-Dimethylphenyl)formamide (3), 4-Nitrocatechol (4), Methylsuccinic acid (5), Phenyllactic acid (6) and 5,6-Dimethylbenzimidazole (7). Moreover, 4-(Diethylamino)salicylaldehyde exhibited the most potent inhibitory effect against Rhizoctonia solani, with an EC50 value of 14.487 mg/L, while 4-Nitrosodiphenylamine showed great antibacterial activity against Erwinia amylovora, with an EC50 value of 5.715 mg/L. This study successfully isolated several highly active antimicrobial compounds from the metabolites of the strain KN37, which could contribute as scaffolds for subsequent chemical synthesis. On the other hand, the newly predicted antibiotic-like substances have not yet been isolated, but they still hold significant research value. They are instructive in the study of active natural product biosynthetic pathways, activation of silent gene clusters, and engineering bacteria construction.

Wheat protein‐derived surfactants: Synthesis and properties

AbstractGreen surfactants produced from peptides and their derivatives have excellent surface chemistry and application properties. A mild, biocompatible, and rapidly biodegradable green surfactant, potassium N‐lauroyl wheat peptide (PLW), was synthesized by an acylation method in the aqueous phase with lauryl chloride and wheat oligopeptide as starting materials. Furthermore, the isoelectric point, equilibrium surface tension, dynamic surface tension, micellar aggregation behavior, foaming, and irritating properties of PLW were studied. Wheat oligopeptides were discovered to have the greatest glutamic acid content, accounting for 30.92% of the overall amino acid composition. The findings revealed that the protonation and ionization behavior of PLW was pH dependent. At pH 8.5, water's surface tension was lowered to 32.1 mN/m−1. At high concentrations and pH, PLW formed large aggregates in solution, causing the adsorption behavior of PLW molecules to shift from diffusion‐controlled adsorption to mixed kinetic adsorption, with PLW exhibiting great surface activity. Furthermore, PLW has good foaming properties and is non‐irritating. As a result, PLW is predicted to become widely employed in the field of household chemicals.

Cs4PMo11VO40-Catalyzed Glycerol Ketalization to Produce Solketal: An Efficient Bioadditives Synthesis Method

In this work, a series of vanadium-substituted phosphomolybdic acids were synthesized and tested as the catalysts for the synthesis of solketal, a green fuel bioadditive, from the condensation reaction of glycerol with acetone. The objective was to demonstrate that an easily synthesizable solid catalyst can efficiently promote glycerol condensation with acetone at room temperature. The activity of pristine heteropolyacid (i.e., H3PMo12O40) and its vanadium-substituted cesium salts (Cs3+nPMo12-nVnO40; n = 0–3) was evaluated in condensation reactions carried out at room temperature. Among the catalysts tested, Cs4PMo11VO40 was the most active and selective towards a five-member ring solketal isomer (dioxolane). A high yield of solketal (i.e., 95% conversion and 95% selectivity to solketal) was achieved in glycerol condensation with acetone at room temperature within a short reaction time (2 h). The influence of the main reaction parameters, such as the acetone–glycerol molar ratio, catalyst load, and reaction temperatures, was investigated. The greatest activity of the Cs4PMo11VO40 catalyst was correlated to its greatest acidity.

Sex differences in neural response to an acute stressor in individuals with an alcohol use disorder.

Alcohol use disorder (AUD) and stress influence overlapping neural circuits in the brain. The literature is mixed regarding the presence of sex differences in the neural response to acute stressors, and this issue has not been examined in individuals with AUD. We validated a stress functional magnetic resonance imaging (fMRI) paradigm in individuals with AUD and tested for sex differences. Twenty-five treatment-seeking individuals with AUD (15M/10F) were recruited to participate in the neuroimaging study linked to a clinical trial of ibudilast (NCT03594435). To assess social-evaluative stress, participants completed the Montreal Imaging Stress Task (MIST). Whole brain and amygdala region-of-interest analyses were conducted. Subjective ratings of anxiety and distress were collected. Repeated measures ANCOVAs were performed to evaluate the effect of stress on anxiety and distress and to evaluate sex differences. There were trend-level effects of stress on anxiety ratings and amygdala activation (p's = 0.06). There was a significant effect of stress in the bilateral thalamus, ventral tegmental area, and paracingulate (Z's > 4.09, p's < 0.03). There was a trend-level effect of sex on subjective ratings of stress (p's = 0.07). Females had higher amygdala activation in response to stress (p = 0.02). Females also had greater activation than males in the precuneus, posterior cingulate cortex, and right inferior frontal gyrus during acute stress (Z's > 3.56, p's < 0.03). This study provides an initial validation of the MIST in a sample of individuals with AUD. It also provides preliminary evidence of sex differences in the response to social-evaluative stress, which is important, given the relevance of stress and negative emotionality as motivators for alcohol use in females.

Multistage structural self-supported electrode via structural engineering on carbon nanofibers for efficient hydrogen evolution reaction at high current density

Pt-based catalysts suffered from the wastage of active sites, resulting in unsatisfactory actual catalytic performance and poor durability as non-self-supporting catalysts for alkaline hydrogen evolution reaction (HER). In this work, we designed a self-supporting electrode material with multi-level structure that utilized carbon nanofibers anchored with cobalt to load and stabilize Pt nanoparticles (Pt@Co/CNFs) for achieving high activity and stability in alkaline HER. The carbon nanofibers served as a framework, with cobalt nanoparticles as an electron donor that can transfer electrons to the metal Pt to accelerating water splitting. In addition, the morphology of the multi-level structure surface was controlled by the content of the reducing agent to giving the material excellent superhydrophilic/underwater superaerophobic properties with ultra-low Pt load (0.29 mg cm−2), which was beneficial for HER. HER test results showed that Pt@Co/CNFs exhibited great catalytic activity, with η10 = 15 mV and η100 = 101 mV. Besides, the stable mechanical structure and the stability of the designed catalytic surface and electron donor in the multi-level structure gave the material exceptional stability. During the 100-hour stability test at 100 mA cm−2, the voltage change was only 50 mV. Besides, utilizing the Pt@Co/CNFs self-supporting electrode directly in the AEM water electrolysis system, a cell voltage as low as 2.18 V was achieved at 500 mA cm−2. Impressively, it demonstrated operational stability for over 200 h without noticeable decay. This work provides a promising approach for the development of advanced self-supporting electrode catalysts.

Core-Shell Gold Nanoparticles@Pd-Loaded Covalent Organic Framework for In Situ Surface-Enhanced Raman Spectroscopy Monitoring of Catalytic Reactions.

A core-shell nanostructure of gold nanoparticles@covalent organic framework (COF) loaded with palladium nanoparticles (AuNPs@COF-PdNPs) was designed for the rapid monitoring of catalytic reactions with surface-enhanced Raman spectroscopy (SERS). The nanostructure was prepared by coating the COF layer on AuNPs and then in situ synthesizing PdNPs within the COF shell. With the respective SERS activity and catalytic performance of the AuNP core and COF-PdNPs shell, the nanostructure can be directly used in the SERS study of the catalytic reaction processes. It was shown that the confinement effect of COF resulted in the high dispersity of PdNPs and outstanding catalytic activity of AuNPs@COF-PdNPs, thus improving the reaction rate constant of the AuNPs@COF-PdNPs-catalyzed hydrogenation reduction by 10 times higher than that obtained with Au/Pd NPs. In addition, the COF layer can serve as a protective shell to make AuNPs@COF-PdNPs possess excellent reusability. Moreover, the loading of PdNPs within the COF layer was found to be in favor of avoiding intermediate products to achieve a high total conversion rate. AuNPs@COF-PdNPs also showed great catalytic activities toward the Suzuki-Miyaura coupling reaction. Taken together, the proposed core-shell nanostructure has great potential in monitoring and exploring catalytic processes and interfacial reactions.

Evaluation of bacteriostatic and antioxidant activities of various extracts from aerial part of Piper nigrum grown in Gulf countries traditionally used for the treatment of various infectious diseases

AbstractPiper nigrum (P. nigrum) is a tropical medicinal plant widely available in Southeast Asian countries including Oman. In Asian It has a long history of usage in places such as Oman for treating of rheumatism, colds, and various infections. Based on the medicinal uses, the purpose of this research is to create diverse fractions using increasing solvent polarity from the aerial part of the collected plant species and evaluate their antibacterial and antioxidant activities by using established bioassays. The aerial part was collected from the Southern part of Oman and processed using the standard method. The processed materials were recovered using the maceration method using methanol, and the methanol raw extracts was further fractionated with water extraction, butanol, ethyl acetate (ETA), hexane, and dichloromethane are produced using different liquid polarities. Each of the six plant extracts was tested for antioxidant and antibacterial potential at different concentrations against DPPH (1, 1-diphenyl-2-picrylhydrazyl) and agar diffusion methods. All of the fractions at varied concentrations shown promising antioxidant activity with DPPH against the gallic acid. The maximum activity was observed in hexane extract, while the smallest potential was noticed in butanol extract, in the following order: hexane &gt; chloroform &gt; water &gt; methanol &gt; ethyl acetate &gt; butanol extract. The antibacterial efficacy of six different polarities extracts gives moderate activity against two Gram-positive bacteria strains namely S. saprophyticus and S. aureus and three Gram-negative namely P. vulgaris, K. senegalensis and E. coli. Among the six extracts, hexane extract had the most antibacterial activity, whereas butanol extract had the smallest activity. The remaining four extracts, chloroform, ethyl acetate, methanol, and water, all had comparable activity. In conclusion, the extracts with the greatest activity from the chosen plant types might be employed as natural antioxidants to treat infectious disorders.

Quantum chemistry calculation-aided discovery of potent small-molecule mimics of glutathione peroxidases for the treatment of cisplatin-induced hearing loss

Hearing loss (HL) is a health burden that seriously affects the quality of life of cancer patients receiving platinum-based chemotherapy, and few FDA-approved treatment specifically targets this condition. The main mechanisms that contribute to cisplatin-induced hearing loss are oxidative stress and subsequent cell death, including ferroptosis revealed by us as a new mechanism recently. In this study, we employed the frontier molecular orbital (FMO) theory approach as a convenient prediction method for the glutathione peroxidase (GPx)-like activity of isoselenazolones and discovered new isoselenazolones with great GPx-like activity. Notably, compound 19 exhibited significant protective effects against cisplatin-induced hair cell (HC) damage in vitro and in vivo and effectively reverses cisplatin-induced hearing loss through oral administration. Further investigations revealed that this compound effectively alleviated hair cell oxidative stress, apoptosis and ferroptosis. This research highlights the potential of GPx mimics as a therapeutic strategy against cisplatin-induced hearing loss. The application of quantum chemistry (QC) calculations in the study of GPx mimics sheds light on the development of new, innovative treatments for hearing loss.

Generation and characterization of a nanobody against the avian influenza virus H7 subtype

Avian influenza virus (AIV) H7N9 diseases have been recently reported, raising concerns about a potential pandemic. Thus, there is an urgent need for effective therapeutics for AIV H7N9 infections. Herein, camelid immunization and yeast two-hybrid techniques were used to identify potent neutralizing nanobodies (Nbs) targeting the H7 subtype hemagglutinin. First, we evaluated the binding specificity and hemagglutination inhibition activity of the screened Nbs against the H7 subtype hemagglutinin. Nb-Z77, with high hemagglutination inhibition activity was selected from the screened Nbs to optimize the yeast expression conditions and construct oligomeric forms of Nb-Z77 using various ligation methods. The oligomers Nb-Z77-DiGS, Nb-Z77-TriGS, Nb-Z77-Fc and Nb-Z77-Foldon were successfully constructed and expressed. Nb-Z77-DiGS and Nb-Z77-Foldon exhibited considerably greater activity than did Nb-Z77 against H7 subtype hemagglutinin, with median effective concentrations of 384.7 and 27.33 pM and binding affinity values of 213 and 5.21 pM, respectively. Nb-Z77-DiGS and Nb-Z77-Foldon completely inhibited the hemagglutination activity of the inactivated virus H7-Re1 at the lowest concentration of 0.938 μg/mL. This study screened a strain of Nb with high hemagglutination inhibition activity and enhanced its antiviral activity through oligomerization, which may have great potential for developing effective agents for the prevention, diagnosis, and treatment of AIV H7 subtype infection.

Resistance risk assessment for benzovindiflupyr in Sclerotium rolfsii and transmission of resistance genes among population.

Sclerotium rolfsii is a destructive soil-borne fungal pathogen which is distributed worldwide. In previous study, the succinate dehydrogenase inhibitor (SDHI) fungicide benzovindiflupyr has been identified for its great antifungal activity against Sclerotium rolfsii. This study is aimed to investigate the resistance risk and mechanism of benzovindiflupyr in Sclerotium rolfsii. Eight stable benzovindiflupyr-resistant isolates were generated by fungicide adaptation. Although the obtained eight resistant isolates have a stronger pathogenicity than the parental sensitive isolate, they have a fitness penalty in the mycelial growth and sclerotia formation compared to the parental isolate. A positive cross-resistance existed in the resistant isolates between benzovindiflupyr and thifluzamide, carboxin, boscalid and isopyrazam. Three-point mutations, including SdhBN180D, SdhCQ68E and SdhDH103Y, were identified in the benzovindiflupyr-resistant isolates. However, molecular docking analysis indicated that only SdhDH103Y could influence the sensitivity of Sclerotium rolfsii to benzovindiflupyr. After mycelial co-incubation of resistant isolates and the sensitive isolate, resistance genes may be transmitted to the sensitive isolate. The in vivo efficacy of benzovindiflupyr and thifluzamide against benzovindiflupyr-resistant isolates was a little lower than that against the sensitive isolate but with no significant difference. The results suggested a low to medium resistance risk of Sclerotium rolfsii to benzovindiflupyr. However, once resistance occurs, it is possible to spread in the population of Sclerotium rolfsii. This study is helpful to understanding the risk and mechanism of resistance to benzovindiflupyr in multinucleate pathogens such as Sclerotium rolfsii. © 2024 Society of Chemical Industry.

Functional Status in Peripheral Arterial Disease: Rehabilitated Versus Nonrehabilitated

To analyze patient perception of functional status related to activity and participation of rehabilitated and nonrehabilitated individuals with peripheral arterial disease. Cross-sectional study assessing the activity and participation domain using the Human Activity Profile (HAP) questionnaire and the Participation Scale, respectively. Groups were compared using Chi-squared test and unpaired t-test. A total of 87 individuals (36 rehabilitated) with 65.28±8.29years (66.7% male) were included. HAP classified 58.6% of individuals with weak or inactive physical activity level, and approximately half of the sample did not have participation restriction. HAP scores and Participation Scale (locomotion inside and outside home) were lower in nonrehabilitated than in rehabilitated individuals. Individuals with peripheral arterial disease presented little participation restriction and a great activity limitation, the last one being more evident among nonrehabilitated.