The purpose of this study was to evaluate the effects of therapeutic ultrasound on structural properties and functional performance of Achilles tendon healing. Thirty Sprague-Dawley rats with ...surgical hemitransected Achilles tendon were studied. Ten were treated daily with 1 MHz continuous ultrasound at 1.0 W/cm
2 for 4 min, 11 at 2.0 W/cm
2 for 4 min and nine served as control without treatment. Achilles functional index (AFI) was recorded preoperatively and on postoperative days 3, 10 and 30. On day 30, the rats were sacrificed and Achilles tendons were tested for load-relaxation, stiffness and ultimate tensile strength (UTS). Results showed that UTS of both low-dose (
p = 0.023) and high-dose (
p = 0.002) groups was significantly greater than in controls. No significant differences in AFI (
p = 0.179), load-relaxation (
p = 0.205) and stiffness (
p = 0.842) were found among groups. These findings suggested that both low- and high-dose therapeutic ultrasound accelerate the healing process of ruptured tendon. (E-mail: rsgng@polyu.edu.hk)
Thrombopoietin receptor (TPOR) is a member of the cytokine receptor superfamily expressed primarily on hematopoietic cells. TPOR plays an important role in regulating platelet production. Due to its ...low expression level in human tissue, studies on the biochemical and biophysical properties of TPOR have been limited. In the present study, an extracellular domain of recombinant human TPOR (rh TPOR-EN) was expressed in Escherichia coli as inclusion bodies. Purification was achieved by metal chelated chromatography under denaturing condition and was refolded by gel filtration chromatography. Far UV circular dichroism spectroscopy and surface plasmon resonance experiments were performed to demonstrate that the protein was in a refolded state and could bind with its ligand. Thus, a production and purification scheme was developed by which sufficient quantities of rh TPOR-EN can be made available for biochemical and biophysical characterizations.
The microtubule inhibitor, nocodazole (2.5 mg L super(-1)), can arrest the cell cycle of the pennate diatom Phaeodactylum tricornutum Bohlin at G sub(2) + M phase. Flow cytometric analysis of cells ...treated with nocodazole suggest that the proportion of cells at G sub(2) + M phase can accumulate to over 95%. Even after a 48-h treatment with nocodazole (2.5 mg L super(-1)), the cells can still exit mitosis, suggesting that the cell-cycle arrest is reversible.
This paper presents the challenges of time zero bond integrity for Palladium-coated Copper (Pd-Cu) wire bonding on C65 Aluminium (Al) bond pad low dielectric constant (low-k) wafer with Bond Over ...Active (BOA) pad structure. The LQFP-176 7.9mm×8.5mm, Rough micro Pre-Plated Frame (RμPPF) lead-frame design with the bonding temperature of 240°C on thin 1.45μm Al bond pad thickness test vehicle and 25μm Pd-Cu wire diameter was evaluated in this study. The latest Shinkawa model UTC3000 wire bonder retrofitted with newest Cu kit design and software feature was used to ensure good bondability and Free Air ball (FAB) formation. In consideration of sensitive low-k wafer, 3 types of latest capillary technology from 3 different suppliers were assessed. In combination of the latest Multi-step (M-step) software with gradual bond force steps feature, it demonstrated a promising outcome that fulfilled the time zero bond integrity criteria particularly on one of the capillary. The cross-sectional analysis showed good ball bond of >;25% Al remnant and uniform bond profile. The essential >;75% of Inter-metallic Compound (IMC) coverage is achievable denoting a good ball bond integrity and Al push-out is controllable without shorting to adjacent pad. By de-layering process, no pad damage underneath the bond pad was observed at sample size of 8k pads, suggesting that a lower stress bonded ball was manageable. A spherical shape of FAB was formed as an indication of good ball formation. Other wire bonding process control was also examined and managed to meet the requirements.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in December 2019, causing a respiratory disease (coronavirus disease 2019, COVID-19) of varying severity in Wuhan, China, and ...subsequently leading to a pandemic. The transmissibility and pathogenesis of SARS-CoV-2 remain poorly understood. We evaluate its tissue and cellular tropism in human respiratory tract, conjunctiva, and innate immune responses in comparison with other coronavirus and influenza virus to provide insights into COVID-19 pathogenesis.
We isolated SARS-CoV-2 from a patient with confirmed COVID-19, and compared virus tropism and replication competence with SARS-CoV, Middle East respiratory syndrome-associated coronavirus (MERS-CoV), and 2009 pandemic influenza H1N1 (H1N1pdm) in ex-vivo cultures of human bronchus (n=5) and lung (n=4). We assessed extrapulmonary infection using ex-vivo cultures of human conjunctiva (n=3) and in-vitro cultures of human colorectal adenocarcinoma cell lines. Innate immune responses and angiotensin-converting enzyme 2 expression were investigated in human alveolar epithelial cells and macrophages. In-vitro studies included the highly pathogenic avian influenza H5N1 virus (H5N1) and mock-infected cells as controls.
SARS-CoV-2 infected ciliated, mucus-secreting, and club cells of bronchial epithelium, type 1 pneumocytes in the lung, and the conjunctival mucosa. In the bronchus, SARS-CoV-2 replication competence was similar to MERS-CoV, and higher than SARS-CoV, but lower than H1N1pdm. In the lung, SARS-CoV-2 replication was similar to SARS-CoV and H1N1pdm, but was lower than MERS-CoV. In conjunctiva, SARS-CoV-2 replication was greater than SARS-CoV. SARS-CoV-2 was a less potent inducer of proinflammatory cytokines than H5N1, H1N1pdm, or MERS-CoV.
The conjunctival epithelium and conducting airways appear to be potential portals of infection for SARS-CoV-2. Both SARS-CoV and SARS-CoV-2 replicated similarly in the alveolar epithelium; SARS-CoV-2 replicated more extensively in the bronchus than SARS-CoV. These findings provide important insights into the transmissibility and pathogenesis of SARS-CoV-2 infection and differences with other respiratory pathogens.
US National Institute of Allergy and Infectious Diseases, University Grants Committee of Hong Kong Special Administrative Region, China; Health and Medical Research Fund, Food and Health Bureau, Government of Hong Kong Special Administrative Region, China.
IMPORTANCE: Early onset of myopia is associated with high myopia later in life, and myopia is irreversible once developed. OBJECTIVE: To evaluate the efficacy of low-concentration atropine eyedrops ...at 0.05% and 0.01% concentration for delaying the onset of myopia. DESIGN, SETTING, AND PARTICIPANTS: This randomized, placebo-controlled, double-masked trial conducted at the Chinese University of Hong Kong Eye Centre enrolled 474 nonmyopic children aged 4 through 9 years with cycloplegic spherical equivalent between +1.00 D to 0.00 D and astigmatism less than −1.00 D. The first recruited participant started treatment on July 11, 2017, and the last participant was enrolled on June 4, 2020; the date of the final follow-up session was June 4, 2022. INTERVENTIONS: Participants were assigned at random to the 0.05% atropine (n = 160), 0.01% atropine (n = 159), and placebo (n = 155) groups and had eyedrops applied once nightly in both eyes over 2 years. MAIN OUTCOMES AND MEASURES: The primary outcomes were the 2-year cumulative incidence rate of myopia (cycloplegic spherical equivalent of at least −0.50 D in either eye) and the percentage of participants with fast myopic shift (spherical equivalent myopic shift of at least 1.00 D). RESULTS: Of the 474 randomized patients (mean age, 6.8 years; 50% female), 353 (74.5%) completed the trial. The 2-year cumulative incidence of myopia in the 0.05% atropine, 0.01% atropine, and placebo groups were 28.4% (33/116), 45.9% (56/122), and 53.0% (61/115), respectively, and the percentages of participants with fast myopic shift at 2 years were 25.0%, 45.1%, and 53.9%. Compared with the placebo group, the 0.05% atropine group had significantly lower 2-year cumulative myopia incidence (difference, 24.6% 95% CI, 12.0%-36.4%) and percentage of patients with fast myopic shift (difference, 28.9% 95% CI, 16.5%-40.5%). Compared with the 0.01% atropine group, the 0.05% atropine group had significantly lower 2-year cumulative myopia incidence (difference, 17.5% 95% CI, 5.2%-29.2%) and percentage of patients with fast myopic shift (difference, 20.1% 95% CI, 8.0%-31.6%). The 0.01% atropine and placebo groups were not significantly different in 2-year cumulative myopia incidence or percentage of patients with fast myopic shift. Photophobia was the most common adverse event and was reported by 12.9% of participants in the 0.05% atropine group, 18.9% in the 0.01% atropine group, and 12.2% in the placebo group in the second year. CONCLUSIONS AND RELEVANCE: Among children aged 4 to 9 years without myopia, nightly use of 0.05% atropine eyedrops compared with placebo resulted in a significantly lower incidence of myopia and lower percentage of participants with fast myopic shift at 2 years. There was no significant difference between 0.01% atropine and placebo. Further research is needed to replicate the findings, to understand whether this represents a delay or prevention of myopia, and to assess longer-term safety. TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR-IPR-15006883
Despite causing regular seasonal epidemics with substantial morbidity, mortality and socioeconomic burden, there is still a lack of research into influenza B viruses (IBVs). In this study, we provide ...for the first time a systematic investigation on the tropism, replication kinetics and pathogenesis of IBVs in the human respiratory tract.Physiologically relevant
explant cultures of human bronchus and lung, human airway organoids, and
cultures of differentiated primary human bronchial epithelial cells and type-I-like alveolar epithelial cells were used to study the cellular and tissue tropism, replication competence and induced innate immune response of 16 IBV strains isolated from 1940 to 2012 in comparison with human seasonal influenza A viruses (IAVs), H1N1 and H3N2. IBVs from the diverged Yamagata- and Victoria-like lineages and the earlier undiverged period were included.The majority of IBVs replicated productively in human bronchus and lung with similar competence to seasonal IAVs. IBVs infected a variety of cell types, including ciliated cells, club cells, goblet cells and basal cells, in human airway organoids. Like seasonal IAVs, IBVs are low inducers of pro-inflammatory cytokines and chemokines. Most results suggested a higher preference for the conducting airway than the lower lung and strain-specific rather than lineage-specific pathogenicity of IBVs.Our results highlighted the non-negligible virulence of IBVs which require more attention and further investigation to alleviate the disease burden, especially when treatment options are limited.
Numerous reports of vascular events after an initial recovery from COVID-19 form our impetus to investigate the impact of COVID-19 on vascular health of recovered patients. We found elevated levels ...of circulating endothelial cells (CECs), a biomarker of vascular injury, in COVID-19 convalescents compared to healthy controls. In particular, those with pre-existing conditions (e.g., hypertension, diabetes) had more pronounced endothelial activation hallmarks than non-COVID-19 patients with matched cardiovascular risk. Several proinflammatory and activated T lymphocyte-associated cytokines sustained from acute infection to recovery phase, which correlated positively with CEC measures, implicating cytokine-driven endothelial dysfunction. Notably, we found higher frequency of effector T cells in our COVID-19 convalescents compared to healthy controls. The activation markers detected on CECs mapped to counter receptors found primarily on cytotoxic CD8
T cells, raising the possibility of cytotoxic effector cells targeting activated endothelial cells. Clinical trials in preventive therapy for post-COVID-19 vascular complications may be needed.
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