Reported herein is an unprecedented base‐promoted deborylative alkylation of pyridine N‐oxides using 1,1‐diborylalkanes as alkyl sources. The reaction proceeds efficiently for a wide range of ...pyridine N‐oxides and 1,1‐diborylalkanes with excellent regioselectivity. The utility of the developed method is demonstrated by the sequential C−H arylation and methylation of pyridine N‐oxides. The reaction also can be applied for the direct introduction of a methyl group to 9‐O‐methylquinine N‐oxide, thus it can serve as a powerful method for late‐stage functionalization.
Going to the source: The transition‐metal‐free alkylation of pyridine N‐oxides using 1,1‐diborylalkanes as alkyl sources proceeds efficiently for a wide range of pyridine N‐oxides and 1,1‐diborylalkanes with excellent regioselectivity, thus affording C2‐alkylated pyridines in good yields.
Abstract
Background
Most partial hand amputees experience limited wrist movement. The limited rotational wrist movement deteriorates natural upper limb system related to hand use and the usability of ...the prosthetic hand, which may cause secondary damage to the musculoskeletal system due to overuse of the upper limb affected by repetitive compensatory movement patterns. Nevertheless, partial hand prosthetics, in common, have only been proposed without rotational wrist movement because patients have various hand shapes, and a prosthetic hand should be attached to a narrow space.
Methods
We hypothesized that partial hand amputees, when using a prosthetic hand with a wrist rotation module, would achieve natural upper limb movement muscle synergy and motion analysis comparable to a control group. To validate the proposed prototype design with the wrist rotation module and verify our hypothesis, we compared a control group with partial hand amputees wearing hand prostheses, both with and without the wrist rotation module prototype. The study contained muscle synergy analysis through non-negative matrix factorization (NMF) using surface electromyography (sEMG) and motion analyses employing a motion capture system during the reach-to-grasp task. Additionally, we assessed the usability of the prototype design for partial hand amputees using the Jebsen-Taylor hand function test (JHFT).
Results
The results showed that the number of muscle synergies identified through NMF remained consistent at 3 for both the control group and amputees using a hand prosthesis with a wrist rotation module. In the motion analysis, a statistically significant difference was observed between the control group and the prosthetic hand without the wrist rotation module, indicating the presence of compensatory movements when utilizing a prosthetic hand lacking this module. Furthermore, among the amputees, the JHFT demonstrated a greater improvement in total score when using the prosthetic hand equipped with a wrist rotation module compared to the prosthetic hand without this module.
Conclusion
In conclusion, integrating a wrist rotation module in prosthetic hand designs for partial hand amputees restores natural upper limb movement patterns, reduces compensatory movements, and prevent the secondary musculoskeletal. This highlights the importance of this module in enhancing overall functionality and quality of life.
To provide effective diagnosis and rehabilitation, the evaluation of joint moments during sit-to-stand is essential. The conventional systems for the evaluation, which use motion capture cameras, are ...quite accurate. However, the systems are not widely used in clinics due to their high cost, inconvenience, and the fact they require lots of space. To solve these problems, some studies have attempted to use inertial sensors only, but they were still inconvenient and inaccurate with asymmetric weight-bearing. We propose a novel joint moment estimation system that can evaluate both symmetric and asymmetric sit-to-stands. To make a simplified system, the proposal is based on a kinematic model that estimates segment angles using a single inertial sensor attached to the shank and a force plate. The system was evaluated with 16 healthy people through symmetric and asymmetric weight-bearing sit-to-stand. The results showed that the proposed system (1) has good accuracy in estimating joint moments (root mean square error < 0.110 Nm/kg) with high correlation (correlation coefficient > 0.99) and (2) is clinically relevant due to its simplicity and applicability of asymmetric sit-to-stand.
To provide effective interventions for spasticity, accurate and reliable spasticity assessment is essential. For the assessment, the Modified Tardieu Scale (MTS) has been widely used owing to its ...simplicity and convenience. However, it has poor or moderate accuracy and reliability.
We proposed a novel inertial measurement unit (IMU)-based MTS assessment system to improve the accuracy and reliability of the MTS itself. The proposed system consists of a joint angle calculation algorithm, a function to detect abnormal muscle reaction (a catch and clonus), and a visual biofeedback mechanism. Through spastic knee and ankle joint assessment, the proposed IMU-based MTS assessment system was compared with the conventional MTS assessment system in 28 children with cerebral palsy by two raters.
The results showed that the proposed system has good accuracy (root mean square error < 3.2°) and test-retest and inter-rater reliabilities (ICC > 0.8), while the conventional MTS system has poor or moderate reliability. Moreover, we found that the deteriorated reliability of the conventional MTS system comes from its goniometric measurement as well as from irregular passive stretch velocity.
The proposed system, which is clinically relevant, can significantly improve the accuracy and reliability of the MTS in lower limbs for children with cerebral palsy.
Plants show great potential for producing recombinant proteins in a cost-effective manner. Many strategies have therefore been employed to express high levels of recombinant proteins in plants. ...Although foreign domains are fused to target proteins for high expression or as an affinity tag for purification, the retention of foreign domains on a target protein may be undesirable, especially for biomedical purposes. Thus, their removal is often crucial at a certain time point after translation. Here, we developed a new strategy to produce target proteins without foreign domains. This involved
removal of foreign domains fused to the N-terminus by the small ubiquitin-related modifier (SUMO) domain/SUMO-specific protease system. This strategy was tested successfully by generating a recombinant gene,
, that produced human leukemia inhibitory factor (hLIF) fused to p38, a coat protein of the
; the inclusion of p38 increased levels of protein expression. The recombinant protein was expressed at high levels in the leaf tissue of
. Coexpression of bdSENP1, a SUMO-specific protease, proteolytically released His:hLIF from the full-length recombinant protein in the endoplasmic reticulum of
leaf cells. His:hLIF was purified from leaf extracts
Ni
-NTA affinity purification resulting in a yield of 32.49 mg/kg, and the N-terminal 5-residues were verified by amino acid sequencing. Plant-produced His:hLIF was able to maintain the pluripotency of mouse embryonic stem cells. This technique thus provides a novel method of removing foreign domains from a target protein
.
Urban particulate matter (UPM) causes skin aging and inflammatory reactions by influencing skin cells through the aryl hydrocarbon receptor (AhR) signaling pathway.
(also known as
), a red alga ...belonging to the Bangiaceae family, is an edible red seaweed. Here, we examined the anti-pollutant effect of
water extract. While UPM treatment induced xenobiotic response element (XRE) promoter luciferase activity,
water extract reduced UPM-induced XRE activity. Next, we isolated an active compound from
and identified it as porphyra 334. Similar to the
water extract, porphyra 334 attenuated UPM-induced XRE activity. Moreover, although UPM augmented AhR nuclear translocation, which led to an increase in cytochrome P450 1A1 (CYP1A1) mRNA levels, these effects were reduced by porphyra 334. Moreover, UPM induced the production of reactive oxygen species (ROS) and reduced cell proliferation. These effects were attenuated in response to porphyra 334 treatment. Furthermore, our results revealed that the increased ROS levels induced by UPM treatment induced transient receptor potential vanilloid 1 (TRPV1) activity, which is related to skin aging and inflammatory responses. However, porphyra 334 treatment reduced this reaction by inhibiting ROS production induced by CYP1A1 activation. This indicates that porphyra 334, an active compound of
, attenuates UP-induced cell damage by inhibiting AhR-induced ROS production, which results in a reduction in TRPV1 activation, leading to cell proliferation. This also suggests that porphyra 334 could protect the epidermis from harmful pollutants.
While harmful effects of blue light on skin cells have been recently reported, there are few studies regarding natural products that alleviate its negative effects. Therefore, we investigated ...ameliorating effects of yellow chaste weed (YCW) (
) extract and its components, apigenin and galangin, on blue light-irradiated HaCaT cells. In this study, we found that YCW extract improved the reduced proliferation of HaCaT cells induced by blue light-irradiation and reduced blue light-induced production of reactive oxygen species (ROS) levels. We also found that apigenin and galangin, the main components of YCW extract, showed the same activities as YCW extract. In experiments examining molecular mechanisms of YCW extract and its components such as apigenin and galangin, they all reduced expression of transient receptor potential vanilloid member 1 (TRPV1), its phosphorylation, and calcium ion (Ca
) influx induced by blue light irradiation. In addition, apigenin and galangin regulated phosphorylation of mitogen-activated protein kinases (MAPKs). They also reduced phosphorylation of mammalian sterile 20-like kinase-1/2 (MST-1/2), inducing phosphorylation of Akt (protein kinase B), one downstream molecule of MST-1/2. Moreover, apigenin and galangin promoted translocation of Forkhead box O3 (FoxO3a) from the nucleus to the cytosol by phosphorylating FoxO3a. Besides, apigenin and galangin interrupted blue light influences on expression of nuclear and secretory clusterin. Namely, they attenuated both upregulation of nuclear clusterin and downregulation of secretory clusterin induced by blue light irradiation. We also found that they downregulated apoptotic protein Bcl-2 associated X protein (Bax) and conversely upregulated anti-apoptotic protein B-cell lymphoma 2 (Bcl-2). Collectively, these findings indicate that YCW extract and its components, apigenin and galangin, antagonize the blue light-induced damage to the keratinocytes by regulating TRPV1/clusterin/FoxO3a and MAPK signaling.
Olfactory receptors (ORs), which belong to the G-protein-coupled receptor family, have been widely studied as ectopically expressed receptors in various human tissues, including the skin. However, ...the physiological functions of only a few OR types have been elucidated in skin cells. All-
retinoic acid (ATRA) is a well-known medication for various skin diseases. However, many studies have shown that ATRA can have adverse effects, resulting from the suppression of cell proliferation. Here, we investigated the involvement of OR7A17 in the ATRA-induced suppression of human keratinocyte (HaCaT) proliferation. We demonstrated that OR7A17 is expressed in HaCaT keratinocytes, and its expression was downregulated by ATRA. The ATRA-induced downregulation of OR7A17 was attenuated via RAR α or RAR γ antagonist treatment, indicating that the effects of ATRA on OR7A17 expression were mediated through nuclear retinoic acid receptor signaling. Moreover, we found that the overexpression of OR7A17 induced the proliferation of HaCaT cells while counteracting the antiproliferative effect of ATRA. Mechanistically, OR7A17 overexpression reversed the ATRA-induced attenuation of Ca
entry. Our findings indicated that ATRA suppresses cell proliferation through the downregulation of OR7A17 via RAR α- and γ-mediated retinoid signaling. Taken together, OR7A17 is a potential therapeutic target for ameliorating the anti-proliferative effects of ATRA.
The objective was to evaluate the effectiveness and safety of acupuncture for patients with rotator cuff diseases.There were 12 electronic databases and 3 trial registries searched up to November ...30th, 2019. All randomized trials were eligible, regardless of language, date of publication, or settings. The primary outcomes were pain, shoulder function, and proportion of improved participants assessed within 12 weeks of randomization of the trial. The Cochrane risk of bias for the studies was assessed. Effects sizes were presented as a risk ratio, mean difference, or standardized mean difference with a 95% confidence intervals. Grading of Recommendations Assessment, Development and Evaluation approach was adopted to rate certainty of evidence.Of the 3,686 records screened, 28 randomized trials (2,216 participants) were included in this review. The types of acupuncture included manual acupuncture, dry needling, electroacupuncture, acupotomy, warm needle acupuncture, and fire needle acupuncture. All of the studies had an unclear or high risk of bias related to more than 1 domain. Significant benefits of acupuncture in terms of pain and shoulder function were observed in all comparisons, however, the proportion of improved participants was not described in 2 comparisons. There was substantial heterogeneity among meta-analyzed trials. No serious harm was observed. For primary outcomes, the overall certainty of evidence was very low.There was very low certainty of evidence for the benefits of acupuncture for patients with rotator cuff diseases. The safety of acupuncture remains unclear due to the incompleteness of reporting. Future welldesigned randomized trials with transparent reporting are required.
This study explored the feasibility of development of solubilized amniotic membrane extract (AME) as a potential wound healing substrate with improved efficacy. Bovine amniotic membrane was extracted ...using a mixture of acetic acid and 2-mercaptopropionic acid under sonication, which was followed by the frozen, and then lyophilized processes. The effects of AME on cell migration and growth properties were evaluated from 0 to 24 h of post injury using primary human foreskin fibroblast monolayer culture with one line scratch as an in vitro wound model. Its wound healing efficacy and scar preventive effects were investigated using whole thickness biopsy punch (8 mm) wound model obtained from rabbit ear. Intra dermal injections of AME fluid (10 μl of 1.2 μg/μl) on four wound sites were performed at 1 h pre injury, post 1, 2 and 3 day. The processes and levels of re-epithelialization and dermal regeneration were examined through histological assessment with H–E staining. In cell migration study conducted at 24 h post injury, AME (1.7 μg/ml) treated cells significantly increased wound closure with 54.9 % compared to control. Histological image analysis on AME treated wound sites at 36 days post injury showed properly developed epidermal basal cell layers and weave-like dermal collagen bundles, whereas those of untreated control skin showed over-proliferation of epidermis and aggregated collagen bundles with defected dermal regeneration. The results of this study verified the feasibility of dermal injections of freeze dried AME as a potential wound healing substrate which can promote epidermal and dermal regeneration, while avoiding undesirable hyper-proliferation of damaged tissue.
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