Anti-bacterial, anti-biofilm and synergistic effects of phenazine-based ruthenium(II) complexes.

Antimicrobial resistance has become a global threat to human health, which is coupled with the lack of novel drugs. Metallocompounds have emerged as promising diverse scaffolds for the development of new antibiotics. Herein, we prepared some metal compounds mainly focusing on cis-[Ru(bpy)(dppz)(SO3)(NO)](PF6) (PR02, bpy = 2,2'-bipyridine, dppz = dipyrido[3,2-a:2',3'-c]phenazine), in which phenazinic and nitric oxide ligands along with sulfite conferred some key properties. This compound exhibited a redox potential for bound NO+/0 of -0.252 V (vs. Ag|AgCl) and a high pH for nitrosyl-nitro conversion of 9.16, making the nitrosyl ligand the major species. These compounds were still able to bind to DNA structures. Interestingly, reduced glutathione (GSH) was unable to promote significant NO/HNO release, an uncommon feature of many similar systems. However, this reducing agent was essential to generate superoxide radicals. Antimicrobial studies were carried out using six bacterial strains, where none or very low activity was observed for Gram-negative bacteria. However, PR02 and PR (cis-[Ru(bpy)(dppz)Cl2]) showed high antibacterial activity in some Gram-positive strains (MBC for S. aureus up to 4.9 µmol L-1), where the activity of PR02 was similar to or at least 4-fold better than that of PR. Besides, PR02 showed capacity to inhibit bacterial biofilm formation, a major health issue leading to bacterial tolerance to antibiotics. Interestingly, we also showed that PR02 can function in synergism with the known antibiotic ampicillin, improving their action up to 4-fold even against resistant strains. Altogether, these results showed that PR02 is a promising antimicrobial nitrosyl ruthenium compound combining features beyond its killing action, which deserves further biological studies.

Revisiting the reaction pathways for phospholipid hydrolysis catalyzed by phospholipase A2 with QM/MM methods.

Secreted phospholipase A2 (sPLA2) is a Ca2+-dependent, widely distributed enzyme superfamily in almost all mammalian tissues and bacteria. It is also a critical component of the venom of nearly all snakes, as well as many invertebrate species. In non-venomous contexts, sPLA2 assumes significance in cellular signaling pathways by binding cell membranes and catalyzing ester bond hydrolysis at the sn-2 position of phospholipids. Elevated levels of GIIA sPLA2 have been detected in the synovial fluid of arthritis patients, where it exhibits a pro-inflammatory function. Consequently, identifying sPLA2 inhibitors holds promise for creating highly effective pharmaceutical treatments. Beyond arthritis, the similarities among GIIA sPLA2s offer an opportunity for developing treatments against snakebite envenoming, the deadliest neglected tropical disease. Despite decades of study, the details of PLA2 membrane-binding, substrate-binding, and reaction mechanism remain elusive, demanding a comprehensive understanding of the sPLA2 catalytic mechanism. This study explores two reaction mechanism hypotheses, involving one or two water molecules, and distinct roles for the Ca2+ cofactor. Our research focuses on the human synovial sPLA2 enzyme bound to lipid bilayers of varying phospholipid compositions, and employing adiabatic QM/MM and QM/MM MD umbrella sampling methods to energetically and geometrically characterize the structures found along both reaction pathways. Our studies demonstrate the higher frequency of productive conformations within the single-water pathway, also revealing a lower free energy barrier for hydrolyzing POPC. Furthermore, we observe that the TS of this concerted one-step reaction closely resembles transition state geometries observed in X-ray crystallography complexes featuring high-affinity transition state analogue inhibitors.

Prevalence and antibiotic resistance in bacterial isolates of dogs with ulcerative keratitis in São Paulo State, Brazil.

OBJECTIVE: Identify microorganisms present in canine eyes affected by ulcerative keratitis and assess its resistance profile to available antimicrobial drugs. METHODS: Samples were collected from 88 canine eyes that exhibited ulcerative keratitis. They were identified using MALDI-TOF and subjected to antimicrobial susceptibility testing by disk diffusion. RESULTS: Among the assessed subjects, brachycephalic dogs accounted for 74.48% (50/83) of the evaluated canines. Among the 88 evaluated eyes, 90.9% (80/88) showed positive cultures, with 11.33% (10/88) of the samples isolating more than one species of bacteria. Of all bacterial isolates identified (90), Gram-positive bacteria accounted for 63.33% (57/90), while Gram-negative bacteria constituted 36.66% (33/90), with predominance of Staphylococcus spp. at 35.55% (32/90) being, Staphylococcus pseudintermedius at 68.75% (22/32), and Pseudomonas aeruginosa at 15.55% (14/90), respectively. Staphylococcus spp. exhibited resistance to penicillin (89.29%), sulfadiazine and trimethoprim (60.71%), and tetracycline (67.86%), while doxycycline (88.89%), cefotaxime (85.71%), chloramphenicol (82.14%), gentamicin, and moxifloxacin (78.57%) showed the highest sensitivity rates. Pseudomonas aeruginosa displayed sensitivity (100%) to gentamicin and imipenem, and resistance (8.33%) to norfloxacin, ciprofloxacin, and cefepime. Similarly, the Enterobacteriaceae family showed higher sensitivity to amikacin and gentamicin (88.89%), imipenem (88.24%), and levofloxacin (87.5%), with pronounced resistance to amoxicillin-clavulanate (50%) and cefazolin (47.06%). This highlights multiresistance in 23.33% (21/90) of the isolates. CONCLUSIONS: The most isolated species in canine ulcerative keratitis are S. pseudintermedius and P. aeruginosa. However, other species were also isolated, demonstrating diversity in ocular microbiota infection. There is a high-rate multidrug resistance associated with canine ulcerative keratitis. Nevertheless, these strains exhibited sensitivity to antimicrobials commonly used in veterinary ophthalmology.

Biodegradable electrospun poly(L-lactide-co-ε-caprolactone)/polyethylene glycol/bioactive glass composite scaffold for bone tissue engineering.

The field of tissue engineering has witnessed significant advancements in recent years, driven by the pursuit of innovative solutions to address the challenges of bone regeneration. In this study, we developed an electrospun composite scaffold for bone tissue engineering. The composite scaffold is made of a blend of poly(L-lactide-co-ε-caprolactone) (PLCL) and polyethylene glycol (PEG), with the incorporation of calcined and lyophilized silicate-chlorinated bioactive glass (BG) particles. Our investigation involved a comprehensive characterization of the scaffold's physical, chemical, and mechanical properties, alongside an evaluation of its biological efficacy employing alveolar bone-derived mesenchymal stem cells. The incorporation of PEG and BG resulted in elevated swelling ratios, consequently enhancing hydrophilicity. Thermal gravimetric analysis confirmed the efficient incorporation of BG, with the scaffolds demonstrating thermal stability up to 250°C. Mechanical testing revealed enhanced tensile strength and Young's modulus in the presence of BG; however, the elongation at break decreased. Cell viability assays demonstrated improved cytocompatibility, especially in the PLCL/PEG+BG group. Alizarin red staining indicated enhanced osteoinductive potential, and fluorescence analysis confirmed increased cell adhesion in the PLCL/PEG+BG group. Our findings suggest that the PLCL/PEG/BG composite scaffold holds promise as an advanced biomaterial for bone tissue engineering.

Glucose-Binding Dioclea bicolor Lectin (DBL): Purification, Characterization, Structural Analysis, and Antibacterial Properties.

In this study, we purified a lectin isolated from the seeds of Dioclea bicolor (DBL) via affinity purification. Electrophoresis analysis revealed that DBL had three bands, α, ß, and γ chains, with molecular masses of approximately 29, 14, and 12 kDa, respectively. Gel filtration chromatography revealed that the native form of DBL had a molecular mass of approximately 100 kDa, indicating that it is a tetramer. Interestingly, DBL-induced hemagglutination was inhibited by several glucosides, mannosides, ampicillin, and tetracycline with minimum inhibitory concentration (MIC) values of 1.56-50 mM. Analysis of the complete amino acid sequence of DBL revealed the presence of 237 amino acids with high similarity to other Diocleinae lectins. Circular dichroism showed the prominent ß-sheet secondary structure of DBL. Furthermore, DBL structure prediction revealed a Discrete Optimized Protein Energy (DOPE) score of -26,642.69141/Normalized DOPE score of -1.84041. The DBL monomer was found to consist a ß-sandwich based on its 3D structure. Molecular docking showed the interactions between DBL and α-D-glucose, N-acetyl-D-glucosamine, α-D-mannose, α-methyl-D-mannoside, ampicillin, and tetracycline. In addition, DBL showed antimicrobial activity with an MIC of 125 µg/mL and exerted synergistic effects in combination with ampicillin and tetracycline (fractional inhibitory concentration index ≤ 0.5). Additionally, DBL significantly inhibited biofilm formation and showed no toxicity in murine fibroblasts (p < 0.05). These results suggest that DBL exhibits antimicrobial activity and works synergistically with antibiotics.

Designing for usability: development and evaluation of a portable minimally-actuated haptic hand and forearm trainer for unsupervised stroke rehabilitation.

In stroke rehabilitation, simple robotic devices hold the potential to increase the training dosage in group therapies and to enable continued therapy at home after hospital discharge. However, we identified a lack of portable and cost-effective devices that not only focus on improving motor functions but also address sensory deficits. Thus, we designed a minimally-actuated hand training device that incorporates active grasping movements and passive pronosupination, complemented by a rehabilitative game with meaningful haptic feedback. Following a human-centered design approach, we conducted a usability study with 13 healthy participants, including three therapists. In a simulated unsupervised environment, the naive participants had to set up and use the device based on written instructions. Our mixed-methods approach included quantitative data from performance metrics, standardized questionnaires, and eye tracking, alongside qualitative feedback from semi-structured interviews. The study results highlighted the device's overall ease of setup and use, as well as its realistic haptic feedback. The eye-tracking analysis further suggested that participants felt safe during usage. Moreover, the study provided crucial insights for future improvements such as a more intuitive and comfortable wrist fixation, more natural pronosupination movements, and easier-to-follow instructions. Our research underscores the importance of continuous testing in the development process and offers significant contributions to the design of user-friendly, unsupervised neurorehabilitation technologies to improve sensorimotor stroke rehabilitation.

MMP-1, MMP-8, and MMP-13 Gene Polymorphisms and Haplotype Is a Risk Factor for Dupuytren Contracture: A Case-Control Study.

BACKGROUND: There is an increased tissue expression of matrix metalloproteinases (MMPs) on Dupuytren contracture (DC). Genetic polymorphisms (single nucleotide polymorphism [SNPs]) in genes of these enzymes may individually influence these transcriptions. Haplotype analysis, which is the observation of a group of alleles, could be more useful to identify the association between SNPs and DC. The purpose of this study was to evaluate the influence of MMP-1 g.-1607 G>GG (rs1799750), MMP-8 g.-799 C>T (rs11225395), and MMP-13 g.-77 A>G (rs2252070) SNPs individually and in haplotype on DC. METHODS: A total of 60 patients with a clinical diagnosis of DC were evaluated and matched, according to age and gender, with the control group of 100 patients without this clinical diagnosis. Genomic DNA was extracted from saliva samples, and genotypes were obtained by polymerase chain reaction-restriction fragment length polymorphism. Statistical analysis of the results included Mann-Whitney U test, Chi-squared test, and PHASE and R software, with a significance level of 5%. RESULTS: The 3 SNPs studied showed significant differences in allele and genotype frequencies between the groups: 2G in MMP-1 (P = .018; odds ratio [OR] 1.80 (95% confidence interval [CI], 1.13-2.88)), T in MMP-8 (P = .015; OR 0.53 (95% CI, 0.33-0.88)), and A in MMP-13 (rs2252070) SNPs (P = .040, OR 0.54 (95% CI, 0.33-0.90)) are risk alleles. The global haplotype analysis indicated a significant difference between both groups. CONCLUSIONS: In conclusion, MMP-1 g.-1607 G>GG (rs1799750), MMP-8 g.-799 C>T (rs11225395), and MMP-13 g.-77 A>G (rs2252070) SNPs, individually and in haplotype, are a risk factor for DC, indicating that these SNPs may be a potential diagnostic and prognostic factor for DC.

Evaluating tactile feedback in addition to kinesthetic feedback for haptic shape rendering: a pilot study.

In current virtual reality settings for motor skill training, only visual information is usually provided regarding the virtual objects the trainee interacts with. However, information gathered through cutaneous (tactile feedback) and muscle mechanoreceptors (kinesthetic feedback) regarding, e.g., object shape, is crucial to successfully interact with those objects. To provide this essential information, previous haptic interfaces have targeted to render either tactile or kinesthetic feedback while the effectiveness of multimodal tactile and kinesthetic feedback on the perception of the characteristics of virtual objects still remains largely unexplored. Here, we present the results from an experiment we conducted with sixteen participants to evaluate the effectiveness of multimodal tactile and kinesthetic feedback on shape perception. Using a within-subject design, participants were asked to reproduce virtual shapes after exploring them without visual feedback and with either congruent tactile and kinesthetic feedback or with only kinesthetic feedback. Tactile feedback was provided with a cable-driven platform mounted on the fingertip, while kinesthetic feedback was provided using a haptic glove. To measure the participants' ability to perceive and reproduce the rendered shapes, we measured the time participants spent exploring and reproducing the shapes and the error between the rendered and reproduced shapes after exploration. Furthermore, we assessed the participants' workload and motivation using well-established questionnaires. We found that concurrent tactile and kinesthetic feedback during shape exploration resulted in lower reproduction errors and longer reproduction times. The longer reproduction times for the combined condition may indicate that participants could learn the shapes better and, thus, were more careful when reproducing them. We did not find differences between conditions in the time spent exploring the shapes or the participants' workload and motivation. The lack of differences in workload between conditions could be attributed to the reported minimal-to-intermediate workload levels, suggesting that there was little room to further reduce the workload. Our work highlights the potential advantages of multimodal congruent tactile and kinesthetic feedback when interacting with tangible virtual objects with applications in virtual simulators for hands-on training applications.

Embryonic stem cells overexpressing high molecular weight FGF2 isoform enhance recovery of pre-ganglionic spinal root lesion in combination with fibrin biopolymer mediated root repair.

BACKGROUND: Spinal ventral root avulsion results in massive motoneuron degeneration with poor prognosis and high costs. In this study, we compared different isoforms of basic fibroblast growth factor 2 (FGF2), overexpressed in stably transfected Human embryonic stem cells (hESCs), following motor root avulsion and repair with a heterologous fibrin biopolymer (HFB). METHODS: In the present work, hESCs bioengineered to overexpress 18, 23, and 31 kD isoforms of FGF2, were used in combination with reimplantation of the avulsed roots using HFB. Statistical analysis was conducted using GraphPad Prism software with one-way or two-way ANOVA, followed by Tukey's or Dunnett's multiple comparison tests. Significance was set at *p < 0.05, **p < 0.01, ***p < 0.001, and ****p < 0.0001. RESULTS: For the first set of experiments, rats underwent avulsion of the ventral roots with local administration of HFB and engraftment of hESCs expressing the above-mentioned FGF2 isoforms. Analysis of motoneuron survival, glial reaction, and synaptic coverage, two weeks after the lesion, indicated that therapy with hESCs overexpressing 31 kD FGF2 was the most effective. Consequently, the second set of experiments was performed with that isoform, so that ventral root avulsion was followed by direct spinal cord reimplantation. Motoneuron survival, glial reaction, synaptic coverage, and gene expression were analyzed 2 weeks post-lesion; while the functional recovery was evaluated by the walking track test and von Frey test for 12 weeks. We showed that engraftment of hESCs led to significant neuroprotection, coupled with immunomodulation, attenuation of astrogliosis, and preservation of inputs to the rescued motoneurons. Behaviorally, the 31 kD FGF2 - hESC therapy enhanced both motor and sensory recovery. CONCLUSION: Transgenic hESCs were an effective delivery platform for neurotrophic factors, rescuing axotomized motoneurons and modulating glial response after proximal spinal cord root injury, while the 31 kD isoform of FGF2 showed superior regenerative properties over other isoforms in addition to the significant functional recovery.

Five million years of Antarctic Circumpolar Current strength variability.

The Antarctic Circumpolar Current (ACC) represents the world's largest ocean-current system and affects global ocean circulation, climate and Antarctic ice-sheet stability1-3. Today, ACC dynamics are controlled by atmospheric forcing, oceanic density gradients and eddy activity4. Whereas palaeoceanographic reconstructions exhibit regional heterogeneity in ACC position and strength over Pleistocene glacial-interglacial cycles5-8, the long-term evolution of the ACC is poorly known. Here we document changes in ACC strength from sediment cores in the Pacific Southern Ocean. We find no linear long-term trend in ACC flow since 5.3 million years ago (Ma), in contrast to global cooling9 and increasing global ice volume10. Instead, we observe a reversal on a million-year timescale, from increasing ACC strength during Pliocene global cooling to a subsequent decrease with further Early Pleistocene cooling. This shift in the ACC regime coincided with a Southern Ocean reconfiguration that altered the sensitivity of the ACC to atmospheric and oceanic forcings11-13. We find ACC strength changes to be closely linked to 400,000-year eccentricity cycles, probably originating from modulation of precessional changes in the South Pacific jet stream linked to tropical Pacific temperature variability14. A persistent link between weaker ACC flow, equatorward-shifted opal deposition and reduced atmospheric CO2 during glacial periods first emerged during the Mid-Pleistocene Transition (MPT). The strongest ACC flow occurred during warmer-than-present intervals of the Plio-Pleistocene, providing evidence of potentially increasing ACC flow with future climate warming.

Intraarticular monomethyl fumarate as a perspective therapy for osteoarthritis by macrophage polarization.

BACKGROUND: Osteoarthritis (OA) is a chronic disease that may lead to joint structure degeneration, cartilage destruction, osteophyte formation, subchondral bone disruption, and pain. In this scenario, a higher proportion of the proinflammatory macrophage type 1 (M1) than the anti-inflammatory macrophage type 2 (M2) could be highlighted as a hallmark of OA progression. The balance between these two macrophage types emerges as a new therapeutic target in OA. This study aimed to evaluate the analgesia and macrophage profile in the treatment of experimental osteoarthritis (EOA) with systemic dimethyl fumarate (DMF) or local intra-articular monomethyl fumarate (MMF). RESULTS: DMF via gavage or MMF via intra-articular in the right knee of EOA rats showed improvements in gait parameters and the nociceptive recovery of the mechanical threshold assessment by adapted electronic von Frey treatment on the twenty-first day (long-lasting phase). DMF treatment decreased proinflammatory TNF-α while increasing anti-inflammatory IL-10 cytokines from the macerated capsule on the fifth day (inflammatory phase). MMF treatment showed joint capsule mRNA extraction downregulating iNOS and TNF-α gene expression while upregulating IL-10 and MCP-1. However, CD206 was not significant but higher than untreated EOA rats' joints on the seventh day (inflammatory phase). CONCLUSIONS: Our studies with EOA model induced by MIA suggest a new perspective for human treatment committed with OA based on macrophage polarization as a therapeutic target, switching the proinflammatory profile M1 to the anti-inflammatory profile M2 with DMF systematic or by MMF locally treatment according to the OA severity.

Unveiling chemical responses in the kombucha-based fermentation of black tea, banana flower, and grape juice: LC-ESIMS, GNPS, MS-DIAL, and MS-FINDER-assisted chemical characterization.

The lack of studies evaluating the chemical responses of kombucha microorganisms when exposed to plants is notable in the literature. Therefore, this work investigates the chemical behaviour of 7-, 14- and 21 day-fermentation of kombucha derived from three extracts obtained from banana inflorescence, black tea, and grape juice. After the acquisition of UPLC-ESI-MS data, GNPS molecular networking, MS-Dial, and MS-Finder were used to chemically characterize the samples. The microbial chemical responses were enzymatic hydrolysis, oxidation, and biosynthesis. The biosynthesis was different among the kombucha samples. In fermented black tea, gallic and dihydrosinapic acids were found as hydrolysis products alongside a sugar-derived product namely 7-(α-D-glucopyranosyloxy)-2,3,4,5,6-pentahydroxyheptanoic acid. The sphingolipids, safingol and cedefingol alongside capryloyl glycine and palmitoyl proline were identified. In fermented grapes, sugar degradation and chemical transformation products were detected together with three cell membrane hopanoids characterized as hydroxybacteriohopanetetrol cyclitol ether, (Δ6 or Δ11)-hydroxybacteriohopanetetrol cyclitol ether, and methyl (Δ6 or Δ11)-hydroxybacteriohopanetetrol cyclitol. The fermented banana blossom showed the presence of methyl (Δ6 or Δ11)-hydroxybacteriohopanetetrol cyclitol together with sphingofungin B, sphinganine and other fatty acid derivatives. Parts of these samples were tested for their inhibition against α-glucosidase and their antioxidant effects. Except for the 14-day fermented extracts, other black tea extracts showed significant inhibition of α-glucosidase ranging from 42.5 to 42.8%. A 14-day fermented extract of the banana blossom infusion showed an inhibition of 29.1%, while grape samples were less active than acarbose. The 21-day fermented black tea extract showed moderate antioxidant properties on a DPPH-based model with an EC50 of 5.29 ± 0.10 µg mL-1, while the other extracts were weakly active (EC50 between 80.76 and 168.12 µg mL-1).

Inclusion of exogenous enzymes in feedlot cattle diets: Impacts on physiology, rumen fermentation, digestibility and fatty acid profile in rumen and meat.

The objective of this study was to evaluate if the inclusion of a blend composed of exogenous enzymes (amylase, protease, cellulase, xylanase and beta glucanase) in the individual and combined form in the feedlot steers diet has benefits on the physiology, rumen fermentation, digestibility and fatty acid profile in rumen and meat. The experiment used 24 animals, divided into 4 treatments, described as: T1-CON, T2-BLEND (0.5 g mixture of enzyme), T3-AMIL (0.5 g alpha-amylase), T4-BLEND+AMIL (0.5 g enzyme blend+ 0.5 g amylase). The concentration of mineral matter was higher in the meat of cattle of T4-BLEND+AMIL. A higher proportion of monounsaturated fatty acids was observed in the T3-AMIL group when compared to the others. The percentage of polyunsaturated fatty acids was higher in the T2-BLEND and T4-BLEND+AMIL compared to the T1-CON. The combination of exogenous enzymes in the diet positively modulate nutritional biomarkers, in addition to benefits in the lipid and oxidative profile meat.

Purification, biochemical characterization of a lectin from marine sponge Ircinia strobilina and its effect on the inhibition of bacterial biofilms.

A new lectin from marine sponge Ircinia strobilina, denominated IsL, was isolated by combination of affinity chromatography in Guar gum matrix followed by size exclusion chromatography. IsL was able to agglutinate native and enzymatically treated rabbit erythrocytes, being inhibited by galactosides, such as α-methyl-D-galactopyranoside, ß-methyl-D-galactopyranoside and α-lactose. IsL hemagglutinating activity was stable at neutral to alkaline pH, however the lectin loses its activity at 40° C. The molecular mass determinated by mass spectrometry was 13.655 ± 5 Da. Approximately 40% of the primary structure of IsL was determined by mass spectrometry, but no similarity was observed with any protein. The secondary structure of IsL consists of 28% α-helix, 26% ß-sheet, and 46% random region, as determined by dichroism circular. IsL was a calcium-dependent lectin, but no significant variations were observed by circular dichroism when IsL was incubated in presence of calcium and EDTA. IsL was not toxic against Artemia nauplii and did not have antimicrobial activity against bacterial cells. However, the IsL was able to significantly inhibit the biofilm formation of Staphylococcus aureus and Staphylococcus epidermidis.

Exercise-Induced Muscle Damage after a High-Intensity Interval Exercise Session: Systematic Review.

High-intensity interval training (HIIT) is considered an effective method to improve fitness and health indicators, but its high-intensity exercises and the mechanical and metabolic stress generated during the session can lead to the occurrence of exercise-induced muscle damage. Therefore, this study aimed to describe, by means of a systematic review, the effects of a single HIIT session on exercise-induced muscle damage. A total of 43 studies were found in the Medline/PubMed Science Direct/Embase/Scielo/CINAHL/LILACS databases; however, after applying the exclusion criteria, only 15 articles were considered eligible for this review. The total sample was 315 participants. Among them, 77.2% were men, 13.3% were women and 9.5 uninformed. Their age ranged from 20.1 ± 2 to 47.8 ± 7.5 years. HIIT protocols included running with ergometers (n = 6), CrossFit-specific exercises (n = 2), running without ergometers (n = 3), swimming (n = 1), the Wingate test on stationary bicycles (n = 2), and cycling (n = 1). The most applied intensity controls were %vVO2max, "all out", MV, MAV, Vmax, and HRreserve%. The most used markers to evaluate muscle damage were creatine kinase, myoglobin, and lactate dehydrogenase. The time for muscle damage assessment ranged from immediately post exercise to seven days. HIIT protocols were able to promote changes in markers of exercise-induced muscle damage, evidenced by increases in CK, Mb, LDH, AST, ALT, pain, and muscle circumference observed mainly immediately and 24 h after the HIIT session.

Quantitative and Qualitative Evaluation of Exoskeleton Transparency Controllers for Upper-Limb Neurorehabilitation.

High transparency is a fundamental requirement for upper-limb exoskeletons to promote active patient participation. Although various control strategies have been suggested to improve the transparency of these robots, there are still some limitations, such as the need for precise dynamic models and potential safety issues when external forces are applied to the robot. This study presents a novel hybrid controller designed to tackle these limitations by combining a traditional zero-torque controller with an interaction torque observer that compensates for residual undesired disturbances. The transparency of the proposed controller was evaluated using both quantitative-e.g., residual joint torques and movement smoothness-and qualitative measures-e.g., comfort, agency, and perceived resistance-in a pilot study with six healthy participants. The performance of the new controller was compared to that of two conventional controllers: a zero-torque closed-loop controller and a velocity-based disturbance observer. Our preliminary results show that the proposed hybrid controller may be a good alternative to state-of-the-art controllers as it allows participants to perform precise and smooth movements with low interaction joint torques. Importantly, participants rated the new controller higher in comfort and agency, and lower in perceived resistance. This study highlights the importance of incorporating both quantitative and qualitative assessments in evaluating control strategies developed to enhance the transparency of rehabilitation robots.

Neuroprotection by upregulation of the major histocompatibility complex class I (MHC I) in SOD1G93A mice.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that progressively affects motoneurons, causing muscle atrophy and evolving to death. Astrocytes inhibit the expression of MHC-I by neurons, contributing to a degenerative outcome. The present study verified the influence of interferon ß (IFN ß) treatment, a proinflammatory cytokine that upregulates MHC-I expression, in SOD1G93A transgenic mice. For that, 17 days old presymptomatic female mice were subjected to subcutaneous application of IFN ß (250, 1,000, and 10,000 IU) every other day for 20 days. Rotarod motor test, clinical score, and body weight assessment were conducted every third day throughout the treatment period. No significant intergroup variations were observed in such parameters during the pre-symptomatic phase. All mice were then euthanized, and the spinal cords collected for comparative analysis of motoneuron survival, reactive gliosis, synapse coverage, microglia morphology classification, cytokine analysis by flow cytometry, and RT-qPCR quantification of gene transcripts. Additionally, mice underwent Rotarod motor assessment, weight monitoring, and neurological scoring. The results show that IFN ß treatment led to an increase in the expression of MHC-I, which, even at the lowest dose (250 IU), resulted in a significant increase in neuronal survival in the ALS presymptomatic period which lasted until the onset of the disease. The treatment also influenced synaptic preservation by decreasing excitatory inputs and upregulating the expression of AMPA receptors by astrocytes. Microglial reactivity quantified by the integrated density of pixels did not decrease with treatment but showed a less activated morphology, coupled with polarization to an M1 profile. Disease progression upregulated gene transcripts for pro- and anti-inflammatory cytokines, and IFN ß treatment significantly decreased mRNA expression for IL4. Overall, the present results demonstrate that a low dosage of IFN ß shows therapeutic potential by increasing MHC-I expression, resulting in neuroprotection and immunomodulation.

Metastatic Sertoli cell tumour in a captive giant anteater (Myrmecophaga tridactyla).

There are a few studies on diseases of anteaters, but reports on reproductive lesions and neoplasms of these animals are scarce. This is the first report of a case of metastatic Sertoli cell tumour in a giant anteater (Myrmecophaga tridactyla). The animal had renal lesions associated with impaired renal function as indicated by serum biochemistry. Histopathological and immunohistochemical examinations provided a conclusive diagnosis of Sertoli cell tumour with metastasis to the liver, kidneys and lymph nodes.

Dysglycemia Shapes Visceral Adipose Tissue's Response to GIP, GLP-1 and Glucagon in Individuals with Obesity.

Visceral adipose tissue (VAT) metabolic fingerprints differ according to body mass index (BMI) and glycemic status. Glucagon-like peptide 1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP) and glucagon are gut-associated hormones that play an important role in regulating energy and glucose homeostasis, although their metabolic actions in VAT are still poorly characterized. Our aim was to assess whether GLP-1, GIP and glucagon influence the VAT metabolite profile. To achieve this goal, VAT harvested during elective surgical procedures from individuals (N = 19) with different BMIs and glycemic statuses was stimulated with GLP-1, GIP or glucagon, and culture media was analyzed using proton nuclear magnetic resonance. In the VAT of individuals with obesity and prediabetes, GLP-1 shifted its metabolic profile by increasing alanine and lactate production while also decreasing isoleucine consumption, whereas GIP and glucagon decreased lactate and alanine production and increased pyruvate consumption. In summary, GLP-1, GIP and glucagon were shown to distinctively modulate the VAT metabolic profile depending on the subject's BMI and glycemic status. In VAT from patients with obesity and prediabetes, these hormones induced metabolic shifts toward gluconeogenesis suppression and oxidative phosphorylation enhancement, suggesting an overall improvement in AT mitochondrial function.

Transcriptional Profile of Soybean Seeds with Contrasting Seed Coat Color.

Soybean is the primary source of vegetable protein and is used for various purposes, mainly to feed animals. This crop can have diverse seed coat colors, varying from yellow, black, brown, and green to bicolor. Black seed coat cultivars have already been assigned as favorable for both seed and grain production. Thus, this work aimed to identify genes associated with soybean seed quality by comparing the transcriptomes of soybean seeds with contrasting seed coat colors. The results from RNA-seq analyses were validated with real-time PCR using the cultivar BRS 715A (black seed coat) and the cultivars BRS 413 RR and DM 6563 IPRO (yellow seed coat). We found 318 genes differentially expressed in all cultivars (freshly harvested seeds and seeds stored in cold chamber). From the in silico analysis of the transcriptomes, the following genes were selected and validated with RT-qPCR: ACS1, ACSF3, CYP90A1, CYP710A1, HCT, CBL, and SAHH. These genes are genes induced in the black seed coat cultivar and are part of pathways responsible for ethylene, lipid, brassinosteroid, lignin, and sulfur amino acid biosynthesis. The BRSMG 715A gene has almost 4times more lignin than the yellow seed coat cultivars. These attributes are related to the BRSMG 715A cultivar's higher seed quality, which translates to more longevity and resistance to moisture and mechanical damage. Future silencing studies may evaluate the knockout of these genes to better understand the biology of soybean seeds with black seed coat.