Cardiomyopathy is a common and lethal complication in patients with limb-girdle muscular dystrophy (LGMD), one of the most prevalent forms of muscular dystrophy. The pathogenesis underlying ...LGMD-related cardiomyopathy remains unclear. NRIP (gene name DCAF6), a Ca2+-dependent calmodulin binding protein, was reduced in dystrophic muscles from LGMD patients. Mice lacking NRIP exhibit a myopathic phenotype resembling that in LGMD patients, making NRIP deficiency a potential culprit leading to cardiomyopathy. This study aimed to determine if NRIP deficiency leads to cardiomyopathy and to explore the underlying molecular mechanisms.
NRIP expression was reduced in both human and mouse failing hearts. Muscle-specific NRIP knockout (MCK-Cre::Dcaf6flox/flox) mouse heart and isolated cardiomyocytes exhibited markedly reduced contractility. Transmission electron microscopy revealed abnormal sarcomere structures and mitochondrial morphology in MCK-Cre::Dcaf6flox/flox hearts. Protein co-immunoprecipitation and confocal imaging revealed that NRIP interacts with α-actinin 2 (ACTN2) at the Z-disc. We found that NRIP facilitated ACTN2-mediated F-actin bundling, and that NRIP deficiency resulted in reduced binding between Z-disc proteins ACTN2 and Cap-Z. In addition, NRIP-deficiency led to increased mitochondrial ROS and impaired mitochondrial respiration/ATP production owing to elevated cellular NADH/NAD+ ratios. Treatment with mitochondria-directed antioxidant mitoTEMPO or NAD+ precursor nicotinic acid restored mitochondrial function and cardiac contractility in MCK-Cre::Dcaf6flox/flox mice.
NRIP is essential to maintain sarcomere structure and mitochondrial/contractile function in cardiomyocytes. Our results revealed a novel role for NRIP deficiency in the pathogenesis of LGMD and heart failure. Targeting NRIP, therefore, could be a powerful new approach to treat myocardial dysfunction in LGMD and heart failure patients.
•NRIP is reduced in the dystrophic muscles of LGMD patients and in the failing heart.•NRIP deficiency leads to abnormal sarcomere structures and mitochondrial ROS levels.•NRIP binds α-actinin 2 at Z-disc and is required for Cap-Z/α-actinin interaction.•Normalizing mitochondrial ROS and NADH/NAD+ restores NRIP-deficient heart function.•Targeting NRIP could be a powerful new approach for cardiac dysfunction in LGMD.
SARS-CoV-2 could trigger multiple immune responses, leading to several autoimmune diseases, including thyroid diseases. Many cases of thyroid diseases caused by COVID-19 infection have been reported. ...Here, we describe the disease development of patients with autoimmune thyroid disease after COVID-19 infection.
The clinical characteristics, diagnosis and treatment of five different patients with autoimmune thyroid disease after COVID-19 infection were reported.
Female patients with primary autoimmune thyroid disease which have been stable for many years were reported. One month after COVID-19 infection, the disease has undergone different evolution. Case 1, a patient with history of long-term stable Hashimoto's thyroiditis, suddenly suffered from Graves disease after COVID-19 infection. Case 2, a patient with history of long-term stable Hashimoto's thyroiditis with thyroid nodules, suddenly suffered from Graves disease after infection. Case 3, a patient with history of long-term stable Graves disease, suddenly suffered from worsening after infection. The above three cases showed thyroid-stimulating antibodies were enhanced. Case 4, a patient with history of previous hypothyroidism had an increase in thyroid-related antibody (TPOAb and TRAb) activity after infection, followed by a marked worsening of hypothyroidism. Case 5, a patient with no history of thyroid disease suddenly developed controllable "thyrotoxicosis" after infection, suggesting the diagnosis of painless thyroiditis.
The five case reports show a different development of the primary autoimmune thyroid disease after COVID-19 infection. The change in the trend of thyroid disease is closely related to the immune response induced by SARS-CoV-2 infection.
This letter investigates the mechanism of abnormal substrate current (Isub) after hot carrier stress (HCS) in fin field effect transistors (FinFETs). Traditionally, after HCS, the drain current and ...Isub of the saturation region will continue to decrease. In this work, however, Isub first decreased and then exhibited a gradual abnormal rise. This abnormal Isub behavior was investigated by different measurement methods and was determined to be due to trap-assisted tunneling. This study first uses different operating voltages to prove the proposed model, then applies a variable temperature stress condition to confirm the model. Finally, a junction current measurement is used to determine the location of defect generation.
In Taiwan, herbal tea is considered a traditional medicine and has been consumed for hundreds of years. In contrast to regular tea, herbal teas are prepared using plants other than the regular tea ...plant, Camellia sinensis (L.) Kuntze. Bitter tea (kǔ-chá), a series of herbal teas prepared in response to common diseases in Taiwan, is often made from local Taiwanese plants. However, the raw materials and formulations have been kept secret and verbally passed down by store owners across generations without a fixed recipe, and the constituent plant materials have not been disclosed.
The aim was to determine the herbal composition of bitter tea sold in Taiwan, which can facilitate further studies on pharmacological applications and conserve cultural resources.
Interviews were conducted through a semi-structured questionnaire. The surveyed respondents were traditional sellers of traditional herbal tea. The relevant literature was collated for a systematic analysis of the composition, characteristics, and traditional and modern applications of the plant materials used in bitter tea. We also conducted an association analysis of the composition of Taiwanese bitter tea with green herb tea (qing-cao-cha tea), another commonly consumed herbal tea in Taiwan, as well as herbal teas in neighboring areas outside Taiwan.
After visiting a total of 59 stores, we identified 32 bitter tea formulations and 73 plant materials. Asteraceae was the most commonly used family, and most stores used whole plants. According to a network analysis of nine plant materials used in high frequency as drug pairs, Tithonia diversifolia and Ajuga nipponensis were found to be the core plant materials used in Taiwanese bitter tea.
Plant materials used in Taiwanese bitter tea were distinct, with multiple therapeutic functions. Further research is required to clarify their efficacy and mechanisms.
Many e-commerce websites currently provide online reviews to share e-shoppers’ experience with the products. To help e-shoppers obtaining information efficiently, these websites usually summarize ...product information based on their certain predefined aspects. However, e-shopper’s aspects should be annotated to make sure that more highly related information of online reviews can be fetched for fulfilling e-shopper’s requirements. Hence, this study integrates an annotation approach with similarity techniques (Keyword pair similarity and Aspect-sentence similarity) to propose a new framework to fetch more highly correlated sentences for e-shoppers. Experimental results show that most of the combinations in the proposed approach have high prediction performance in the Top 10 sentences with Precision (0.90 or higher).
Augmented reality (AR) is an emerging technology that allows users to interact with simulated environments, including those emulating scenes in the real world. Most current AR technologies involve ...the placement of virtual objects within these scenes. However, difficulties in modeling real-world objects greatly limit the scope of the simulation, and thus the depth of the user experience. In this study, we developed a process by which to realize virtual environments that are based entirely on scenes in the real world. In modeling the real world, the proposed scheme divides scenes into discrete objects, which are then replaced with virtual objects. This enables users to interact in and with virtual environments without limitations. An RGB-D camera is used in conjunction with simultaneous localization and mapping (SLAM) to obtain the movement trajectory of the user and derive information related to the real environment. In modeling the environment, graph-based segmentation is used to segment point clouds and perform object segmentation to enable the subsequent replacement of objects with equivalent virtual entities. Superquadrics are used to derive shape parameters and location information from the segmentation results in order to ensure that the scale of the virtual objects matches the original objects in the real world. Only after the objects have been replaced with their virtual counterparts in the real environment converted into a virtual scene. Experiments involving the emulation of real-world locations demonstrated the feasibility of the proposed rendering scheme. A rock-climbing application scenario is finally presented to illustrate the potential use of the proposed system in AR applications.
Subchondral bone deterioration and osteophyte formation attributable to excessive mineralization are prominent features of end-stage knee osteoarthritis (OA). The cellular events underlying ...subchondral integrity diminishment remained elusive. This study was undertaken to characterize subchondral mesenchymal stem cells (SMSCs) isolated from patients with end-stage knee OA who required total knee arthroplasty. The SMSCs expressed surface antigens CD29, CD44, CD73, CD90, CD105, and CD166 and lacked CD31, CD45, and MHCII expression. The cell cultures exhibited higher proliferation and greater osteogenesis and chondrogenesis potencies, whereas their population-doubling time and adipogenic lineage commitment were lower than those of bone marrow MSCs (BMMSCs). They also displayed higher expressions of embryonic stem cell marker OCT3/4 and osteogenic factors Wnt3a, β-catenin, and microRNA-29a (miR-29a), concomitant with lower expressions of joint-deleterious factors HDAC4, TGF-β1, IL-1β, TNF-α, and MMP3, in comparison with those of BMMSCs. Knockdown of miR-29a lowered Wnt3a expression and osteogenic differentiation of the SMSCs through elevating HDAC4 translation, which directly regulated the 3′-untranslated region of HDAC4. Likewise, transgenic mice that overexpressed miR-29a in osteoblasts exhibited a high bone mass in the subchondral region. SMSCs in the transgenic mice showed a higher osteogenic differentiation and lower HDAC4 signaling than those in wild-type mice. Taken together, high osteogenesis potency existed in the SMSCs in the osteoarthritic knee. The miR-29a modulation of HDAC4 and Wnt3a signaling was attributable to the increase in osteogenesis. This study shed an emerging light on the characteristics of SMSCs and highlighted the contribution of SMSCs in the exacerbation of subchondral integrity in end-stage knee OA.
Key messages
Subchondral MSCs (SMSCs) from OA knee expressed embryonic stem cell marker Oct3/4.
The SMSCs showed high proliferation and osteogenic and chondrogenic potencies.
miR-29a regulated osteogenesis of the SMSCs through modulation of HDAC4 and Wnt3a.
A high osteogenic potency of the SMSCs existed in mice overexpressing miR-29a in bone.
Aberrant osteogenesis in SMSCs provides a new insight to subchondral damage in OA.
Purpose
Collaboration with universities is an important innovation strategy for enterprises. However, currently very little research has focused on how such university-industry collaborative ...innovation activities should be managed. The paper aims to discuss this issue.
Design/methodology/approach
This paper introduces the university-industry collaborative innovation practices of Zhejiang NHU Company in China. By using a case study as the method, this paper aims to illustrate the mechanism of university-industry collaborative innovation and how to manage the collaborative innovation activities efficiently.
Findings
Zhejiang NHU Company established a university-industry collaborative innovation link through three innovation platforms: the technology R&D center, the ZJU-NHU joint-research center, and the national engineer center. Zhejiang NHU Company manages its collaborative relationships with universities through this innovation network.
Originality/value
NHU Company managed the collaborative relationship efficiently with the institutions, representing an effective degree of university-industry collaborative innovation management.
Soil microbes play an important role in the ecosystem and have a relationship with plant growth, development, and production. There are only a few reports on the effects of planting patterns of ...cassava on the microbial community structure in the rhizospheric soil. Here, we investigated the effects of different fertilization on the microbial community structure in the cassava rhizospheric soil. SC205 cultivar was used in this study as the experimental material. Compound fertilizer (CF) and reduced fertilizer (RF) were applied to the soil prior to planting. Soil samples were collected before harvest, and fungi were analyzed using IonS5
TM
XL sequencing platform. Results showed that CF and RF treatments significantly increased cassava yield. Amplicon sequencing result indicated that the fungi richness in rhizospheric soil of cassava was increased after CF was applied, and the diversity was decreased. However, the fungal diversity and richness were decreased in rhizospheric soil after RF was applied. The most dominant fungal phylum was Ascomycota, which increased after fertilization. In addition, the abundance of beneficial fungi such as
Chaetomium
increased after fertilization, while that of pathogenic fungi such as
Fusarium solani
was decreased. The composition of the fungal community in rhizospheric soil with CF and RF applied was similar, but the richness and diversity of fungi were different. Canonical correspondence analysis (CCA) indicates there was a positive correlation between soil nutrition and fungal community structure. Overall, our results indicate that fertilization alters the fungal community structure of cassava rhizospheric soil, such that the abundance of potentially beneficial fungi increased, while that of potentially pathogenic fungi decreased, thereby significantly promoting plant growth and yield of cassava. Thus, during actual production, attention should be paid to maintain the stability of cassava rhizospheric soil micro-ecology.
Lymphadenopathy with increased immunoglobulin (Ig) G4 + plasma cells can be a nonspecific finding or a manifestation of immunoglobulin G4-related disease (IgG4-RD). It remains unclear whether there ...are characteristic pathologic features of IgG4-RD involving lymph nodes, or if IgG4-RD lymphadenopathy can occur without other manifestations of IgG4-RD. In this study, we assessed 55 lymph node biopsy specimens (44 men and 11 women with a mean age of 55 y) with increased IgG4 + plasma cells that had 1 of the 6 well-described pathologic patterns. We also correlated these findings with IgG4 serum levels and followed these patients for 7 to 108 months (mean, 34.9 mo) for the occurrence of extranodal IgG4-RD. We further compared lymphadenopathy in patients who developed other manifestations of IgG4-RD (RD + , n=20, 36%) versus those who did not (RD - , n=35, 64%). We found that there were only minor significant differences between 2 groups, including frequency of receiving treatment (RD + , 90% vs. RD - , 60%, P =0.021) and higher serum levels of C-reactive protein (>8 mg/L, RD + , 53% vs. RD - , 13%, P =0.007). Other differences were either borderline or not significant, including mean age (RD + , 59.8 y vs. RD - , 51.9 y, P =0.097), male-to-female ratio (RD + , 16:4 vs. RD - , 28:7, P =1), constitutional symptoms (RD + , 25% vs. RD - , 9%, P =0.096), multiple enlarged lymph nodes (RD + , 45% vs. RD - , 26%, P =0.143), good response to therapy (RD + , 94% vs. RD - , 94%, P =1); higher serum IgG4 levels (>280 mg/dL, RD + , 75% vs. RD - , 51%, P =0.086), anemia (RD + , 45% vs. RD - , 43%, P =0.877), leukopenia (RD + , 0% vs. RD - , 3%, P =0.446), thrombocytopenia (RD + , 10% vs. RD - , 6%, P =0.556), positivity for antinuclear antibody (RD + , 24% vs. RD - , 29%, P =0.688), elevated serum levels of lactate dehydrogenase (>225 U/L, RD + , 0% vs. RD - , 20%, P =0.064), elevated serum IgE level (>100 IU/mL, RD + , 75% vs. RD - , 92%, P =0.238), and hypergammaglobulinemia (RD + , 90% vs. RD - , 86%, P =0.754). There were also no differences in morphologic patterns ( P =0.466), IgG4 + cell location ( P =0.104), eosinophil counts (RD + , 10.3±11.3 vs. RD - , 13.4±17.5, P =0.496), Epstein-Barr virus positivity (RD + , 35% vs. RD - , 60%, P =0.074), and Epstein-Barr virus-positive cell location ( P =0.351). Our findings suggest that there are minimal differences between stringently defined IgG4-RD lymphadenopathy with versus without other manifestations of IgG4-RD. These findings also suggest the existence of IgG4-RD lymphadenopathy as the sole presentation of IgG4-RD.
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