The emergence of SARS-CoV-2 variants of concern with progressively increased transmissibility between humans is a threat to global public health. The Omicron variant of SARS-CoV-2 also evades ...immunity from natural infection or vaccines
, but it is unclear whether its exceptional transmissibility is due to immune evasion or intrinsic virological properties. Here we compared the replication competence and cellular tropism of the wild-type virus and the D614G, Alpha (B.1.1.7), Beta (B.1.351), Delta (B.1.617.2) and Omicron (B.1.1.529) variants in ex vivo explant cultures of human bronchi and lungs. We also evaluated the dependence on TMPRSS2 and cathepsins for infection. We show that Omicron replicates faster than all other SARS-CoV-2 variants studied in the bronchi but less efficiently in the lung parenchyma. All variants of concern have similar cellular tropism compared to the wild type. Omicron is more dependent on cathepsins than the other variants of concern tested, suggesting that the Omicron variant enters cells through a different route compared with the other variants. The lower replication competence of Omicron in the human lungs may explain the reduced severity of Omicron that is now being reported in epidemiological studies, although determinants of severity are multifactorial. These findings provide important biological correlates to previous epidemiological observations.
Recently, gold nanoparticles (Au NPs) have been used to study the treatment of malignant tumors due to their higher biocompatibility and lesser toxicity. In addition, they can be excited through a ...specific wavelength to produce oscillating plasmonic photothermal therapy (PPTT) on the basis of the localized surface plasma resonance (LSPR) effect. Au NPs can be heated to kill cancer cells in specific parts of the body in a noninvasive manner. In this study, branched gold nanoparticles (BAu NPs) were prepared by mixing HAuCl
in a 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES) buffer solution in a molar ratio of 1:2000. The UV-vis absorption peak was detected in the range of 700-1000 nm. Subsequently, BAu NPs were chemically linked to a thiol-modified mannoside molecule via a stable sulfur-Au covalent bond (Man@BAu NPs). Due to the presence of abundant mannose receptors on human-breast-cancer cells, MDA-MB-231, Man@BAu NPs were found to be abundant inside cancer cells. After irradiating the Man@BAu NP-laden MDA-MB231 switch with a near-infrared (NIR) laser at 808 nm wavelength, the photothermal-conversion effect raised the surface temperature of Man@BAu NPs, thus inducing cell death. Our experiment results demonstrated the advantages of applying Man@BAu NPs in inducing cell death in MDA-MB-231.
Thioridazine (THD) is a common phenothiazine antipsychotic drug reported to suppress growth in several types of cancer cells. We previously showed that THD acts as an antiglioblastoma and anticancer ...stem-like cell agent. However, the signaling pathway underlying autophagy and apoptosis induction remains unclear. THD treatment significantly induced autophagy with upregulated AMPK activity and engendered cell death with increased sub-G1 in glioblastoma multiform (GBM) cell lines. Notably, through whole gene expression screening with THD treatment, frizzled (Fzd) proteins, a family of G-protein-coupled receptors, were found, suggesting the participation of Wnt/β-catenin signaling. After THD treatment, Fzd-1 and GSK3β-S9 phosphorylation (inactivated form) was reduced to promote β-catenin degradation, which attenuated P62 inhibition. The autophagy marker LC3-II markedly increased when P62 was released from β-catenin inhibition. Additionally, the P62-dependent caspase-8 activation that induced P53-independent apoptosis was confirmed by inhibiting T-cell factor/β-catenin and autophagy flux. Moreover, treatment with THD combined with temozolomide (TMZ) engendered increased LC3-II expression and caspase-3 activity, indicating promising drug synergism. In conclusion, THD induces autophagy in GBM cells by not only upregulating AMPK activity, but also enhancing P62-mediated autophagy and apoptosis through Wnt/β-catenin signaling. Therefore, THD is a potential alternative therapeutic agent for drug repositioning in GBM.
Introduction
Resilience has been associated with psychological adaptation to many threatening life events, but previous studies have rarely analysed the integrated relationships among demographic and ...disease characteristics and various health outcomes in Taiwan. This study examined the associations among demographic factors, disease characteristics, resilience, coping styles and adverse health outcomes, including anxiety and depressive symptoms and sleep disorders.
Methods
A descriptive, cross‐sectional study design was used. Data from a convenience sample of 175 patients with breast cancer aged 20 years or older were collected using a self‐reported questionnaire. A structural equation modelling approach was applied to examine the relationships among the variables.
Results
The results showed that greater resilience was related to fewer depressive symptoms, lower anxiety levels and better sleep quality. All three coping styles, including active coping, minimising the situation and avoidance coping, were negatively correlated with depressive symptoms, but only active coping was significantly correlated with sleep quality. Resilience had a direct effect on depressive symptoms, anxiety and sleep disorders. Furthermore, a mediating effect of resilience was observed on the relationship between marital satisfaction and depressive symptoms.
Conclusion
Resilience can strengthen breast cancer‐related adaptation. Additionally, breast cancer survivors who used mainly the active and minimising coping styles tended to experience fewer depressive symptoms.
Knowledge of human anatomy is vital for nurses. Medical educators use a variety of educational pedagogies, including the use of cadavers, to cultivate nursing students into competent and professional ...care providers and to help them gain authentic experience and knowledge before entering the workplace. Studies have provided numerous examples of students with positive learning experiences in human‐centric (humanistic) anatomy courses; however, whether these positive experiences translate into effective clinical practice remains largely unknown. This study explored nurses' perspectives on the effects of a humanistic anatomy program on their nursing practice. Focus groups with semi‐structured interview guidelines were conducted to collect data. Twenty‐one nurses working in hospitals in Taiwan participated and divided themselves into four groups on the basis of willingness to participate and availability. The interviews were recorded using smartphones, and the recordings were transcribed using a computer. The transcriptions were then checked word by word artificially and analyzed by hand. Three main themes emerged during the analysis: adapting to the professional journey, managing time when providing humanistic care, and cultivating professionalism. The results demonstrate educators' expectations that humanistic anatomy education for nursing students expands students' professional knowledge and helps them develop humanistic competencies as professional nurses.
Lethal toxin (LT) is the critical virulence factor of
, the causative agent of anthrax. One common symptom observed in patients with anthrax is thrombocytopenia, which has also been observed in mice ...injected with LT. Our previous study demonstrated that LT induces thrombocytopenia by suppressing megakaryopoiesis, but the precise molecular mechanisms behind this phenomenon remain unknown. In this study, we utilized 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced megakaryocytic differentiation in human erythroleukemia (HEL) cells to identify genes involved in LT-induced megakaryocytic suppression. Through cDNA microarray analysis, we identified Dachshund homolog 1 (
) as a gene that was upregulated upon TPA treatment but downregulated in the presence of TPA and LT, purified from the culture supernatants of
. To investigate the function of DACH1 in megakaryocytic differentiation, we employed short hairpin RNA technology to knock down DACH1 expression in HEL cells and assessed its effect on differentiation. Our data revealed that the knockdown of DACH1 expression suppressed megakaryocytic differentiation, particularly in polyploidization. We demonstrated that one mechanism by which
LT induces suppression of polyploidization in HEL cells is through the cleavage of MEK1/2. This cleavage results in the downregulation of the ERK signaling pathway, thereby suppressing
gene expression and inhibiting polyploidization. Additionally, we found that known megakaryopoiesis-related genes, such as
,
,
,
,
, and
genes may be positively regulated by
. Furthermore, we observed an upregulation of DACH1 during in vitro differentiation of CD34-megakaryocytes and downregulation of DACH1 in patients with thrombocytopenia. In summary, our findings shed light on one of the molecular mechanisms behind LT-induced thrombocytopenia and unveil a previously unknown role for DACH1 in megakaryopoiesis.
Aim. The aim of this paper is to report an investigation of the effects of soft music on sleep quality in older community‐dwelling men and women in Taiwan.
Background. Sleep is a complex rhythmic ...state that may be affected by the ageing process. Few studies have focused on the effects of music, a non‐pharmacological method of improving the quality of sleep in older adults.
Method. A randomized controlled trial was used with a two‐group repeated measures design.
Sixty people aged 60–83 years with difficulty in sleeping were recruited through community leaders and screened using the Pittsburgh Sleep Quality Index (PSQI) and Epworth Sleepiness Scale. Those reporting depression, cognitive impairment, medical or environmental problems that might interfere with sleep; and those who used sleeping medications, meditation, or caffeine at bedtime were excluded. Participants listened to their choice among six 45‐minute sedative music tapes at bedtime for 3 weeks. There were five types of Western and one of Chinese music. Sleep quality was measured with the PSQI before the study and at three weekly post‐tests. Groups were comparable on demographic variables, anxiety, depressive symptoms, physical activity, bedtime routine, herbal tea use, napping, pain, and pretest overall sleep quality.
Results. Music resulted in significantly better sleep quality in the experimental group, as well as significantly better components of sleep quality: better perceived sleep quality, longer sleep duration, greater sleep efficiency, shorter sleep latency, less sleep disturbance and less daytime dysfunction (P = 0·04–0·001). Sleep improved weekly, indicating a cumulative dose effect.
Conclusion. The findings provide evidence for the use of soothing music as an empirically‐based intervention for sleep in older people.
Quercetin and crocin are the main active constituents of Eucommia and Gardenia species, respectively. This study was conducted to explore the effects of quercetin and crocin on fat reduction and ...renal fibrosis and the relationship of these compounds with autophagy. First, a model of high-fat diet- and streptozotocin-induced type 2 diabetes was established and then subjected model animals to 8 weeks of metformin, quercetin and crocin gavage. Then, a high glucose-induced rat mesangial cells (RMCs) model was established, and these cells were cocultured with quercetin and crocin. The results showed that quercetin and crocin can decrease fasting blood glucose levels, reduce fat accumulation in the liver, alleviate renal fibrosis, and reduce blood lipid levels. Quercetin and crocin increased autophagy-related protein (LC3, Atg5, Beclin-1 and p-AMPK) levels in the liver and decreased autophagy-related protein (LC3, Atg5, Beclin-1 and p-AMPK) levels in the kidneys. Moreover, quercetin and crocin inhibited the excessive proliferation of RMCs induced by high-glucose (HG) conditions, decreased autophagy-related protein (LC3, Atg5, Beclin-1 and p-AMPK) levels, and decreased TGF-β1 expression. Importantly, cotreatment with quercetin and crocin had a more significant effect than treatment with either compound alone. These results suggest that combined administration of quercetin and crocin can more significantly reduce blood glucose/lipid levels and improve renal fibrosis than administration of either compound alone and that AMPK-dependent autophagy might be involved in this process. Eucommia ulmoides Oliv. and Gardenia could be developed as drugs for Type 2 diabetes treatment.
Aims
This study examined the relationship among upgrades in academic qualifications, practice accreditations, self‐efficacy, outcome expectations and nurses' career interest.
Background
Interest in ...the nursing career could help retain nurses in the nursing profession. A global nurse shortage warrants further research to understand what drives interest in the nursing career.
Methods
A cross‐sectional design was employed. Data were collected in a medical centre in Northern Taiwan between February and March 2017, using employee records and a survey instrument. Proportionate random sampling was used to identify full‐time registered nurses, of whom 524 provided useable responses. Employee records were used to measure nurses' upgrades in academic qualifications and practice accreditation.
Results
Upgrades in academic qualifications and upgrades in practice accreditation are positively related to outcome expectations. Both self‐efficacy and outcome expectations are positively related to career interest.
Conclusion
The pursuit of upgrades in academic qualifications and practice accreditation could enhance nurses' outcome expectations, thus enhancing their interest in a nursing career.
Implications for Nursing Management
Hospital managers could develop policies, procedures and programmes to encourage nurses to enhance their academic qualifications or practice accreditation, helping enhance their interest in remaining in the nursing career.
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