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Numerous rheumatologic autoimmune diseases, among which rheumatoid arthritis, are chronic inflammatory diseases capable of inducing multiple cumulative articular and extra-articular damage, if not properly treated. Nevertheless, benign conditions may, similarly, exhibit arthritis as their major clinical finding, but with short-term duration instead, and evolve to spontaneous resolution in a few days to weeks, without permanent articular damage. Such distinction—self-limited arthritis with no need of immunosuppressive treatment or chronic arthritis at early stages?—represents one of the greatest challenges in clinical practice, once many metabolic, endocrine, neoplastic, granulomatous, infectious diseases and other autoimmune conditions may mimic rheumatoid arthritis. Indeed, the diagnosis of rheumatoid arthritis at early stages is a crucial step to a more effective mitigation of the disease-related damage. As a prototype of chronic inflammatory autoimmune disease, rheumatoid arthritis has been linked to oxidative stress, a condition in which the pool of reactive oxygen species increases over time, either by their augmented production, the reduction in antioxidant defenses, or the combination of both, ultimately implying compromise in the redox signaling. The exact mechanisms through which oxidative stress may contribute to the initiation and perpetuation of local (in the articular milieu) and systemic inflammation in rheumatoid arthritis, particularly at early stages, still remain to be determined. Furthermore, the role of antioxidants as therapeutic adjuvants in the control of disease activity seems to be overlooked, as a little number of short studies addressing this issue is currently found. Thus, the present review focuses on the binomial rheumatoid arthritis-oxidative stress, bringing insights into their pathophysiological relationships, as well as the implications of potential diagnostic oxidative stress biomarkers and therapeutic interventions directed to the oxidative status in patients with rheumatoid arthritis.

Background During the past few years, the first industrial-scale cellulosic ethanol plants have been inaugurated. Although the performance of the commercial cellulase enzymes used in this process has greatly improved over the past decade, cellulases still represent a very significant operational cost. Depending on the region, transport of cellulases from a central production facility to a biorefinery may significantly add to enzyme cost. The aim of the present study was to develop a simple, cost-efficient cellulase production process that could be employed locally at a Brazilian sugarcane biorefinery. Results Our work focused on two main topics: growth medium formulation and strain improvement. We evaluated several Brazilian low-cost industrial residues for their potential in cellulase production. Among the solid residues evaluated, soybean hulls were found to display clearly the most desirable characteristics. We engineered a Trichoderma reesei strain to secrete cellulase in the presence of repressing sugars, enabling the use of sugarcane molasses as an additional carbon source. In addition, we added a heterologous β-glucosidase to improve the performance of the produced enzymes in hydrolysis. Finally, the addition of an invertase gene from Aspegillus niger into our strain allowed it to consume sucrose from sugarcane molasses directly. Preliminary cost analysis showed that the overall process can provide for very low-cost enzyme with good hydrolysis performance on industrially pre-treated sugarcane straw. Conclusions In this study, we showed that with relatively few genetic modifications and the right growth medium it is possible to produce considerable amounts of well-performing cellulase at very low cost in Brazil using T. reesei. With further enhancements and optimization, such a system could provide a viable alternative to delivered commercial cellulases.

Background The path for the development of hypersecreting strains of Trichoderma reesei capable of producing industrially relevant enzyme titers remains elusive despite over 70 years of research and industrial utilization. Herein, we describe the rational engineering of the publicly available T. reesei RUT-C30 strain and a customized process for cellulase production based on agroindustrial by-products. Results A CRISPR/Cas9 system was used to introduce six genetic modifications in RUT-C30. Implemented changes included the constitutive expression of a mutated allele of the cellulase master regulator XYR1, the expression of two heterologous enzymes, the β-glucosidase CEL3A from Talaromyces emersonii and the invertase SUC1 from Aspergillus niger, and the deletion of genes encoding the cellulase repressor ACE1 and the extracellular proteases SLP1 and PEP1. These alterations resulted in a remarkable increase of protein secretion rates by RUT-C30 and amended its well described β-glucosidase deficiency while enabling the utilization of sucrose and eliminating the requirement of inducing sugars for enzyme production. With a developed sugarcane molasses-based bioprocess, the engineered strain reached an extracellular protein titer of 80.6 g L−1 (0.24 g L−1 h−1), which is the highest experimentally supported titer so far reported for T. reesei. The produced enzyme cocktail displayed increased levels of cellulase and hemicellulase activities, with particularly large increments being observed for the specific activities of β-glucosidase (72-fold) and xylanase (42-fold). Notably, it also exhibited a saccharification efficiency similar to that of a commercially available cellulase preparation in the deconstruction of industrially pretreated sugarcane straw. Conclusion This work demonstrates the rational steps for the development of a cellulase hyperproducing strain from a well-characterized genetic background available in the public domain, the RUT-C30, associated with an industrially relevant bioprocess, paving new perspectives for Trichoderma research on cellulase production.

Lithium-ion batteries (LIBs) are commonly used in laptops, cell phones, and electric cars and present critical metals such as cobalt, lithium, and nickel in their composition. This article is intended to help researchers working on LIB characterization. It studies three cylindrical LIBs which were dismantled and characterized. The batteries were initially discharged by coupling Ni-Cr resistance wires and then manually dismantled using Buehler IsoMet 1000 cutter and pliers. Then, the batteries were dried at 60°C for 24 h for electrolyte evaporation; the mass loss was considered the electrolyte mass. Morphological analyses of the electrodes were performed using SEM-EDS. The external metal structures and separators were determined by XRD and FTIR, respectively. Digestion of the electrodes in aqua regia followed by EDXRF and AAS analyses was carried out for chemical quantification. The batteries were determined to be NCA, NMC 811, and LFP; the separators were determined to be polypropylene; the metallic shells were Fe-Cr stainless steel. A preliminary economic evaluation for each battery was performed to show the battery type with the greatest market trend, emphasizing the importance of LIB recycling processes. NMC 811 earned the highest price (US$/ton) for its combined metals and hence received the most market attention.

Angiogenesis is the formation of new blood vessel from existing vessels and is a critical first step in tissue repair following chronic disturbances in healing and degenerative tissues. Chronic pathoanatomic tissues are characterized by a high number of inflammatory cells; an overexpression of inflammatory mediators; such as tumor necrosis factor-α (TNF-α) and interleukin-1 (IL-1); the presence of mast cells, T cells, reactive oxygen species, and matrix metalloproteinases; and a decreased angiogenic capacity. Multiple studies have demonstrated that autologous orthobiological cellular preparations (e.g., platelet-rich plasma (PRP)) improve tissue repair and regenerate tissues. There are many PRP devices on the market. Unfortunately, they differ greatly in platelet numbers, cellular composition, and bioformulation. PRP is a platelet concentrate consisting of a high concentration of platelets, with or without certain leukocytes, platelet-derived growth factors (PGFs), cytokines, molecules, and signaling cells. Several PRP products have immunomodulatory capacities that can influence resident cells in a diseased microenvironment, inducing tissue repair or regeneration. Generally, PRP is a blood-derived product, regardless of its platelet number and bioformulation, and the literature indicates both positive and negative patient treatment outcomes. Strangely, the literature does not designate specific PRP preparation qualifications that can potentially contribute to tissue repair. Moreover, the literature scarcely addresses the impact of platelets and leukocytes in PRP on (neo)angiogenesis, other than a general one-size-fits-all statement that “PRP has angiogenic capabilities”. Here, we review the cellular composition of all PRP constituents, including leukocytes, and describe the importance of platelet dosing and bioformulation strategies in orthobiological applications to initiate angiogenic pathways that re-establish microvasculature networks, facilitating the supply of oxygen and nutrients to impaired tissues.

Working towards the development of robust motion recognition systems for assistive technology control, the widespread approach has been to use a plethora of, often times, multi-modal sensors. In this paper, we develop single-sensor motion recognition systems. Utilising the peripheral nature of surface electromyography (sEMG) data acquisition, we optimise the information extracted from sEMG sensors. This allows the reduction in sEMG sensors or provision of contingencies in a system with redundancies. In particular, we process the sEMG readings captured at the trapezius descendens and platysma muscles. We demonstrate that sEMG readings captured at one muscle contain distinct information on movements or contractions of other agonists. We used the trapezius and platysma muscle sEMG data captured in able-bodied participants and participants with tetraplegia to classify shoulder movements and platysma contractions using white-box supervised learning algorithms. Using the trapezius sensor, shoulder raise is classified with an accuracy of 99%. Implementing subject-specific multi-class classification, shoulder raise, shoulder forward and shoulder backward are classified with a 94% accuracy amongst object raise and shoulder raise-and-hold data in able bodied adults. A three-way classification of the platysma sensor data captured with participants with tetraplegia achieves a 95% accuracy on platysma contraction and shoulder raise detection.

This study examines the effects of coastal upwelling on the longitudinal water density gradient within the estuary of Baía de Todos os Santos (BTS), its effect on the gravitational circulation at the estuary entrance, and the reverse effect of gravitational circulation on the coastal upwelling. This investigation was based on a 1-year dataset of observed water temperature, mean velocities, and river discharge, as well as 2 years of numerical simulation of the estuarine flow. The results show that the upwelling regulates the thermohaline field in front of the BTS, decreasing water temperature (up to 3 °C), and increasing density (up to 0.3 kg/m3), and have sufficient intensity to more than double the speed, or even establish, the gravitational circulation. It was frequently observed that the water temperature falls after an increase in the subtidal flow shear, suggesting that the estuarine gravitational circulation acts as a facilitator to the upwelling process. Numerical simulations indicate that the coastal upwelling events are also capable of reestablishing the gravitational circulation at times with weak longitudinal density gradient, a scenario that tends to become more frequent and intense in the near future due to the ongoing climate changes.

Individuals with complete cervical spinal cord injury suffer from a permanent paralysis of upper limbs which prevents them from achieving most of the activities of daily living. We developed a neuroprosthetic solution to restore hand motor function. Electrical stimulation of the radial and median nerves by means of two epineural electrodes enabled functional movements of paralyzed hands. We demonstrated in two participants with complete tetraplegia that selective stimulation of nerve fascicles by means of optimized spreading of the current over the active contacts of the multicontact epineural electrodes induced functional and powerful grasping movements which remained stable over the 28 days of implantation. We also showed that participants were able to trigger the activation of movements of their paralyzed limb using an intuitive interface controlled by voluntary actions and that they were able to perform useful functional movements such as holding a can and drinking through a straw.

Nonalcoholic fatty liver disease (NAFLD) has been considered a novel component of the metabolic syndrome (MetS), with the oxidative stress participating in its progression. This study aimed to evaluate the metabolic profile in young and old mice with MetS, and the effects of apocynin and tempol on glycemic and lipid parameters. Young and old C57BL/6 mice with high fat diet- (HFD-) induced MetS received apocynin and tempol 50 mg·kg−1/day in their drinking water for 10 weeks. After HFD, the young group showed elevated fasting glucose, worsened lipid profile in plasma, steatosis, and hepatic lipid peroxidation. Nevertheless, the old group presented significant increase in fasting insulin levels, insulin resistance, plasma and hepatic lipid peroxidation, and pronounced steatosis. The hepatic superoxide dismutase and catalase activity did not differ between the groups. Tempol and apocynin seemed to prevent hepatic lipid deposition in both groups. Furthermore, apocynin improved glucose tolerance and insulin sensitivity in old mice. In summary, old mice are more susceptible to HFD-induced metabolic changes than their young counterparts. Also, the antioxidant therapy improved insulin sensitivity and glucose tolerance, and in addition, apocynin seemed to prevent the HFD-induced hepatic fat deposition, suggesting an important role of oxidative stress in the induction of NAFLD.

Morton's neuroma is a compressive neuropathy of the common plantar digital nerve, causing significant pain and limiting patients' activities. This study aimed to investigate the effect of pulsed radiofrequency (PRF) on the pain, functionality, and quality of life experienced by patients with Morton's neuroma. This was a prospective study with pre- and post-intervention assessments after one, 3, and 6 months of treatment. The orthopedics department of an affiliated hospital. Patients with Morton's neuroma underwent treatment with ultrasound-guided PRF in 2 sites around the neuroma for 8 minutes. Clinical outcomes were assessed using the visual analog scale (VAS), the American Orthopedic Foot and Ankle Society (AOFAS) questionnaire for assessing foot function, and the Short Form-36 (SF-36) for quality of life. A total of 20 patients (29 feet) completed the 6-month minimum follow-up period. The VAS and face scale values at follow-up were statistically lower than the pre-procedure VAS scores (P < 0.05). The AOFAS and SF-36 values at follow-up were statistically higher than the pre-procedure values (P < 0.05). No significant adverse events were recorded during the follow-up. The prospective research features a limited follow-up duration and lacks an additional group, whether control or treatment, for result comparisons. Applications of PRF decreased the pain and the improved functionality and quality of life experienced by patients with Morton's neuroma for a 6-month follow-up at minimum.