With the rapid development of ultra-high-voltage (UHV) direct-current (DC) transmissions, the impact of static electric fields (SEF) in the vicinity of overhead UHV DC transmission lines on health ...has aroused much public concern. This study explored the effects of 56.3kV/m SEF on the spleen of mice. Results showed that SEF exposure of 21days significantly increased malonic dialdehyde content, superoxide dismutase activity, calcineurin activity, nitric oxide synthase (NOS) activity, and the mRNA expression levels of tumor necrosis factor-α (TNF-α) and nuclear factor-κB (NF-κB) in the spleen and caused the separation of nucleus and nuclear membrane, the disappearance of mitochondrial membrane, and the deficiency of mitochondrial cristae in splenic lymphocytes. By analysis and discussion, it was deduced that SEF could induce oxidative stress of the spleen by increasing the activity of NOS. Oxidative stress could further cause ultrastructural changes of splenic lymphocytes. Moreover, oxidative stress could cause the increase of the mRNA expression levels of TNF-α and NF-κB, which contributed to the occurrence of spleen inflammation.
N
6
-methyladenosine (m
6
A) is the most prevalent mRNA internal modification and has been shown to regulate the development, physiology, and pathology of various tissues. However, the functions of ...the m
6
A epitranscriptome in the visual system remain unclear. In this study, using a retina-specific conditional knockout mouse model, we show that retinas deficient in
Mettl3
, the core component of the m
6
A methyltransferase complex, exhibit structural and functional abnormalities beginning at the end of retinogenesis. Immunohistological and single-cell RNA sequencing (scRNA-seq) analyses of retinogenesis processes reveal that retinal progenitor cells (RPCs) and Müller glial cells are the two cell types primarily affected by
Mettl3
deficiency. Integrative analyses of scRNA-seq and MeRIP-seq data suggest that m
6
A fine-tunes the transcriptomic transition from RPCs to Müller cells by promoting the degradation of RPC transcripts, the disruption of which leads to abnormalities in late retinogenesis and likely compromises the glial functions of Müller cells. Overexpression of m
6
A-regulated RPC transcripts in late RPCs partially recapitulates the
Mettl3
-deficient retinal phenotype. Collectively, our study reveals an epitranscriptomic mechanism governing progenitor-to-glial cell transition during late retinogenesis, which is essential for the homeostasis of the mature retina. The mechanism revealed in this study might also apply to other nervous systems.
The retina is a layer in the eye that converts light into electrical signals, which allows us to see. It is a part of the central nervous system and is made of brain cells, such as neurons and supporting cells called glia. These supporting cells protect neurons, supply them with nutrients and maintain steady surrounding conditions. The retina shares many characteristics with other neural tissues, so it is useful for biologists to study these structures.
One way for cells to control the activity of genes is by chemically modifying messenger RNA molecules. These alterations can affect various aspects of mRNA and the proteins that are ultimately produced. The most common mRNA modification, referred to as m
6
A, plays a key role in the development and healthy performance of various tissues. However, it is unclear whether m
6
A is involved in how glial cells in the retina develop.
To address this question, Xin et al. studied the impact of blocking m
6
A in the retina of mice. These genetically modified mice displayed abnormalities as the retina developed. Analysis of the mRNA produced in single cells and the pattern of modifications revealed that m
6
A is involved in the development of glia. In particular, m
6
A helps to remove the mRNA associated with early-stage proto-glia, allowing the cells to mature and transition to their final form.
The finding by Xin et al. that the m
6
A RNA modification is an essential part of retina development could help to understand eye diseases. In addition, this discovery may apply to other brain regions, and, in time, such work could lead to new treatments for neurodegenerative diseases.
Depression and anxiety are common comorbidities in cardiovascular clinic outpatients. Timely identification and intervention of these mental and psychological disorders can contribute to correct ...diagnosis, better prognosis, less medical expenses, and improved quality of life. The convenience of online doctor-patient communication platforms has increasingly attracted patients to online consultations. However, online health care and offline health care are very different. Research on how to identify psychological disorders in patients who engage in an online cardiology consultation is lacking. This study aimed to explore the feasibility of using a self-rating scale to assess mental illness among patients who consult with a cardiologist online and to compare the differences in anxiety and depression between online and offline patients. From June 2022 to July 2022, we conducted follow-up visits with 10,173 patients on the Haodf platform. We conducted detailed consultations with 286 patients who visited the same cardiologist in the outpatient department. We used the self-rated Generalized Anxiety Disorder (GAD-7) and Patient Health Questionnaire (PHQ-9) scales to assess anxiety and depression, respectively. We analyzed the influencing factors related to the degree of coordination of online patients. We also compared the prevalence of anxiety or depression between online and offline patients and analyzed the factors related to anxiety or depression. Of the 10,173 online consultation patients, only 186 (1.8%) responded effectively. The response rate of the offline consultation patients was 96.5% (276/286). Frequent online communication and watching live video broadcasts were significantly related to effective responses from online patients (P<.001). The prevalence of anxiety (70/160, 43.7% vs 69/266, 25.8%; P<.001) or depression (78/160, 48.7% vs 74/266, 27.7%; P<.001) in online consultation patients was significantly higher than that in offline patients. In bivariate analyses, the factors related to anxiety included female sex, unemployment, no confirmed cardiovascular disease, and the online consultation mode, while smokers and those who underwent COVID-19 quarantine were less likely to present with anxiety. The factors related to depression included female sex, divorced or separated individuals, and the online consultation mode. COVID-19 quarantine was related with a lower likelihood of depression. BMI was negatively correlated with depression. In multiple ordered logistic regression analysis, women were more likely than men to present with anxiety (odds ratio OR 2.181, 95% CI 1.365-3.486; P=.001). Women (OR 1.664, 95% CI 1.082-2.559; P=.02) and online patients (OR 2.631, 95% CI 1.305-5.304; P=.007) were more likely to have depression. Online patients had more anxiety or depression than offline patients. Anxiety was more prevalent in women, the unemployed, and those without confirmed cardiovascular disease. Women and divorced or separated individuals were more prone to depression. Increasing the frequency of doctor-patient communication and participating in video interactions can help improve patient cooperation.
The single edge notch specimen (SEN) is commonly used to measure the fracture toughness, or critical energy release rate of soft elastic materials. To measure toughness, an expression for the energy ...release rate,
J
, the mechanical energy available for growing the crack per unit area, is needed. Since strains in these fracture experiments can easily exceed several hundred percent, large deformation analysis is needed to calculate
J
. An approximate formula for
J
in SEN samples subjected to moderately large deformation was given by Rivlin and Thomas in J Polym Sci 10:291–318.
https://doi.org/10.1002/pol.1953.120100303
(1953) and Greensmith in J Appl Polymer Sci 7:993–1002.
https://doi.org/10.1002/app.1963.070070316
(1963). However, this formula works only for small crack lengths, for stretch ratio up to two and does not match the linear elastic result in the limit of small strains. In this paper we carry out a series of finite element (FE) simulations to obtain accurate approximations that are valid for all practical crack lengths and strain levels. Our FE result shows that the small crack approximation of by Rivlin and Thomas in J Polym Sci 10:291–318.
https://doi.org/10.1002/pol.1953.120100303
(1953) does not work well in the small strain regime, and in particular, result of Greensmith in J Appl Polymer Sci 7:993–1002.
https://doi.org/10.1002/app.1963.070070316
(1963) underestimates the energy release rate for stretch ratios less than 1.5.
Abstract In the context of the epidemic, the daily routines of China’s elderly populace underwent substantial transformations. The implementation of home-based pandemic containment strategies led to ...heightened levels of social isolation and loneliness, exerting a discernible influence on the subjective well-being of this demographic. Consequently, residing in retirement apartments has emerged as a more advantageous alternative for elderly individuals capable of self-care. To meet their life and emotional needs and improve their sense of well-being, we used the KANO model to design a health management app for the self-care of older persons. We summarised the functional requirements for the self-care of elderly people, distributed questionnaires to generate a list of requirements, and conducted data analysis. We optimised the low-fidelity prototype based on the usability test results combined with relevant interface design elements to implement emotional interaction design practices for older persons’ self-care. Furthermore, we completed a design evaluation and program optimisation of the design practice to guide the final visual design. The research findings identify the core principles of interactive design for elderly users to enable visual design specifications for improving the lives of the elderly population. This research highlights the need to design more appropriate products that meet demographic characteristics. This work contributes to strengthening the connection between elderly people and society while bridging the ‘digital divide’ based on this population’s cautious approach to technologies and declining abilities to learn.
Mitochondrial DNA depletion syndrome (MDS) is a group of severe inherited disorders caused by mutations in genes, such as deoxyribonucleoside kinase (DGUOK). A great majority of DGUOK mutant MDS ...patients develop iron overload progressing to severe liver failure. However, the pathological mechanisms connecting iron overload and hepatic damage remains uncovered. Here, two patients’ skin fibroblasts are reprogrammed to induced pluripotent stem cells (iPSCs) and then corrected by CRISPR/Cas9. Patient‐specific iPSCs and corrected iPSCs‐derived high purity hepatocyte organoids (iHep‐Orgs) and hepatocyte‐like cells (iHep) are generated as cellular models for studying hepatic pathology. DGUOK mutant iHep and iHep‐Orgs, but not control and corrected one, are more sensitive to iron overload‐induced ferroptosis, which can be rescued by N‐Acetylcysteine (NAC). Mechanically, this ferroptosis is a process mediated by nuclear receptor co‐activator 4 (NCOA4)‐dependent degradation of ferritin in lysosome and cellular labile iron release. This study reveals the underlying pathological mechanisms and the viable therapeutic strategies of this syndrome, and is the first pure iHep‐Orgs model in hereditary liver diseases.
Iron overload is an important feature in deoxyribonucleoside kinase mutant mitochondrial DNA depletion syndrome. A combined model of patient‐specific induced pluripotent stem cells‐derived liver organoids and hepatocytes reveals a sensitivity to iron overload‐induced ferroptosis in patients. This ferroptosis is a process by NCOA4‐dependent degradation of ferritin in lysosome and cellular labile iron release.
Abstract
Background:
To investigate the Coronavirus Disease 2019 (COVID-19) vaccination coverage and the influential factors of vaccination among patients with mental disorders, we conducted a ...cross-sectional study in China.
Method:
The anonymous questionnaires including demographic data, vaccination status, intention to be vaccinated and its reasons were collected in the Second Xiangya Hospital, one of the biggest four psychiatric centers in China. Mental health of these participants were measured by the Patient Health Questionnaire (PHQ-9) and the Generalized Anxiety Disorder-7 items (GAD-7). The influential factors associated with vaccination status were analyzed by Fisher exact tests and binary logistical analysis.
Result:
1328 patients and 922 family members completed the survey. The vaccination rate of patients included was 69.4%, whereas 85.5% patients were willing to be vaccinated. Being hospitalized (aOR 0.41, 95% CI:0.27–0.60), suffering from schizophrenia (aOR 0.38, 95% CI: 0.19–0.75) and secondary school educational background (aOR 0.58, 95% CI: 0.37–0.93) were significantly associated with less likelihood to get vaccinated. Uptaking vaccines could reduce depressive (aOR 0.63, 95% CI: 0.41–0.98) or anxious symptoms (aOR 0.40, 95% CI: 0.25–0.63) in these patients for a short period.
Conclusion:
Further COVID-19 immunization programme should prioritize hospitalized psychiatric patients and schizophrenic patients since their demands for vaccination had been partly ignored during the current inoculation.
Atrial fibrillation (AF) is highly prevalent in the population, yet the factors contributing to AF events in susceptible individuals remain partially understood. The potential relationship between ...meteorological factors and AF, particularly with abnormal electrocardiograph (ECG) repolarization, has not been adequately studied. This case-crossover study aims to investigate the association between meteorological factors and daily hospital visits for AF with abnormal ECG repolarization in Shanghai, China.
The study cohort comprised 10,325 patients with ECG-confirmed AF who sought treatment at Shanghai Sixth People's Hospital between 2015 and 2018. Meteorological and air pollutant concentration data were matched with the patient records. Using a case-crossover design, we analyzed the association between meteorological factors and the daily count of hospital visitors for AF with abnormal ECG repolarization at our AF center. Lag analysis models were applied to examine the temporal relationship between meteorological factors and AF events.
The analysis revealed statistically significant associations between AF occurrence and specific meteorological factors. AF events were significantly associated with average atmospheric pressure (lag 0 day, OR 0.9901, 95% CI 0.9825-0.9977, P < 0.05), average temperature (lag 1 day, OR 0.9890, 95% CI 0.9789-0.9992, P < 0.05), daily pressure range (lag 7 days, OR 1.0195, 95% CI 1.0079-1.0312, P < 0.01), and daily temperature range (lag 5 days, OR 1.0208, 95% CI 1.0087-1.0331, P < 0.01). Moreover, a significant correlation was observed between daily pressure range and daily temperature range with AF patients, particularly those with abnormal ECG repolarization, as evident in the case-crossover analysis.
This study highlights a significant correlation between meteorological factors and daily hospital visits for AF accompanied by abnormal ECG repolarization in Shanghai, China. In addition, AF patients with abnormal ECG repolarization were found to be more vulnerable to rapid daily changes in pressure and temperature compared to AF patients without such repolarization abnormalities.
In the field of biomedical research, organoids represent a remarkable advancement that has the potential to revolutionize our approach to studying human diseases even before clinical trials. ...Organoids are essentially miniature 3D models of specific organs or tissues, enabling scientists to investigate the causes of diseases, test new drugs, and explore personalized medicine within a controlled laboratory setting. Over the past decade, organoid technology has made substantial progress, allowing researchers to create highly detailed environments that closely mimic the human body. These organoids can be generated from various sources, including pluripotent stem cells, specialized tissue cells, and tumor tissue cells. This versatility enables scientists to replicate a wide range of diseases affecting different organ systems, effectively creating disease replicas in a laboratory dish. This exciting capability has provided us with unprecedented insights into the progression of diseases and how we can develop improved treatments. In this paper, we will provide an overview of the progress made in utilizing organoids as preclinical models, aiding our understanding and providing a more effective approach to addressing various human diseases.
Background
Wohlfahrtiimonas chitiniclastica
is an emerging fly-borne zoonotic pathogen, which causes infections in immunocompromised patients and some animals. Herein, we reported a
W. ...chitiniclastica
BM-Y from a dead zebra in China.
Methods
The complete genome sequencing of BM-Y showed that this isolate carried one chromosome and one novel type of
bla
VEB–1
-carrying plasmid. Detailed genetic dissection was applied to this plasmid to display the genetic environment of
bla
VEB–1
.
Results
Three novel insertion sequence (IS) elements, namely IS
Woch1
, IS
Woch2
, and IS
Woch3
, were found in this plasmid.
aadB
,
aacA1
, and
gcuG
were located downstream of
bla
VEB–1
, composing a gene cassette array
bla
VEB–1
–
aadB
–
aacA1
–
gcuG
bracketed by an intact IS
Woch1
and a truncated one, which was named the
bla
VEB–1
region. The 5′-RACE experiments revealed that the transcription start site of the
bla
VEB–1
region was located in the intact IS
Woch1
and this IS provided a strong promoter for the
bla
VEB–1
region.
Conclusion
The spread of the
bla
VEB–1
-carrying plasmid might enhance the ability of
W. chitiniclastica
to survive under drug selection pressure and aggravate the difficulty in treating infections caused by
bla
VEB–1
-carrying
W. chitiniclastica
. To the best of our knowledge, this is the first report of the genetic characterization of a novel
bla
VEB–1
-carrying plasmid with new ISs from
W. chitiniclastica
.
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