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Protein degradation in eukaryotic cells is mainly carried out by the 26S proteasome, a macromolecular complex not only present in the cytosol and nucleus but also associated with various membranes. How proteasomes are anchored to the membrane and the biological meaning thereof have been largely unknown in higher organisms. Here, we show that N-myristoylation of the Rpt2 subunit is a general mechanism for proteasome-membrane interaction. Loss of this modification in the Rpt2-G2A mutant cells leads to profound changes in the membrane-associated proteome, perturbs the endomembrane system, and undermines critical cellular processes such as cell adhesion, endoplasmic reticulum-associated degradation and membrane protein trafficking. Rpt2G2A/G2A homozygous mutation is embryonic lethal in mice and is sufficient to abolish tumor growth in a nude mice xenograft model. These findings have defined an evolutionarily conserved mechanism for maintaining membrane protein homeostasis and underscored the significance of compartmentalized protein degradation by myristoyl-anchored proteasomes in health and disease.

Background As revealed by previous studies, the head shaking tilt suppression test (HSTST) is associated with the vestibular cerebellum-mediated central storage mechanism and the video head impulse test (vHIT) is crucial for the diagnosis of peripheral vestibular diseases. Objective To explore the clinical application value of HSTST and vHIT in vestibular migraine (VM) and Meniere's disease (MD) . Methods Patients presenting with vertigo or dizziness as the primary complaint and diagnosed with VM and MD were selected from the Neurology Department of the Second People's Hospital of Guiyang from July 2021 to December 2022. After collecting their medical history and performing bedside examinations, pure tone audiometry test was conducted on those with hearing impairment. All patients completed vestibular function tests, including head shaking test (HST), HSTST, caloric test, and vHIT, were performed, followed by calculating the tilt suppression index (TSI). Then the Clinical features and examination results of VM and MD patients with HST positive were compared, and the ROC curve of TSI was plotted to distinguish between the two groups of patients. Results Among the 50 VM patients involved in the study, 22 (44.0%) were HST positive, including 19 (86.4%) exhibiting horizontal nystagmus and 3 (13.6%) showing vertical nystagmus. Among the 45 MD patients, 23 (51.1%) were HST positive, all of whom were horizontal nystagmus. The analysis of the patients with HST positive showed that the female to male ratio in VM and MD patients was 4.5∶1 and 1∶1.3, respectively. The prevalence of family history of headaches was higher in VM patients compared to MD patients (P

The stigma associated with functional neurological disorder (FND) is greater than that associated with other neurological conditions, seriously affecting the quality of life of patients and increasing the burden on caregivers. This article reviews the concept, the current situation and harms, the influence factors and intervention strategies of FND stigma. The aim is to further develop our country as a reference for the study of stigma in FND.

Abstract Obesity is a serious global health issue. Emerging evidence indicates that the gut microbiota may contribute to the development of obesity, possibly by instigating inflammatory processes. The objective of this research is to conduct a comparative analysis of the gut microbiota composition in obese and normal-weight Uygur adults, while examining the associations with adipocyte-related factors and dietary variables. According to the inclusion and exclusion criteria, twenty-seven Uygur adults with obesity and twenty Uygur adults with normal-weight were recruited from a local community. Anthropometric measurements and blood samples were collected. Gut microbiota composition was analyzed using 16 S rRNA gene sequencing. Adipocyte-related factors were measured using enzyme-linked immunosorbent assay (ELISA). Statistical analyses were performed to compare the gut microbiota composition between the two groups and to identify correlations between gut microbiota and adipocyte-related factors. Compared with the normal-weight group, the obese group exhibited a marked reduction in both diversity and richness of the gut microbiota, alongside a decrease in Ruminococcaceae_UCG_014, Coprococcus_2, and Parabacteroides, and an increase in Megamonas and Lachnoclostridium, implying a potential link to the development of obesity. Individuals with obesity were found to have higher Leptin (LEP), Interleukin-6 (IL-6), and C-reactive protein (CRP) than normal-weight individuals. Obese Uygur adults exhibited a gut microbiota characterized by diminished diversity and richness relative to normal-weight individuals. Parabacteroides, Megamonas, and Lachnoclostridium may play an important role in the development of obesity in Uygur population. Underlying mechanisms need further investigation.

Abstract Extreme warm water events, known as marine heatwaves, cause a variety of adverse impacts on the marine ecosystem. They are occurring more and more frequently across the global ocean. Yet monitoring marine heatwaves below the sea surface is still challenging due to the sparsity of in situ temperature observations. Here, we propose a statistical learning method guided by ocean dynamics and optimal prediction theory, to detect subsurface marine heatwaves based on the observable sea surface temperature and sea surface height. This dynamics-guided statistical learning method shows good skills in detecting subsurface marine heatwaves in the oceanic epipelagic zone over many parts of the global ocean. It outperforms both the classical ordinary least square regression and popular deep learning methods that do not effectively exploit ocean dynamics, with clear dynamical interpretation for its outperformance. Our study provides a useful statistical learning method for near real-time monitoring of subsurface marine heatwaves at a global scale and highlights the importance of exploiting ocean dynamics for enhancing the efficiency and interpretability of statistical learning.

Objective To investigate the role of PSMA4 in the prognosis, diagnosis and immune infiltration of lung adenocarcinoma (LUAD), and explore its underlying mechanism. Methods The expression profiles and clinical data of LUAD patients were sourced from the Cancer Genome Atlas (TCGA) database. The expression level of PSMA4 in LUAD tissues (n=539) and normal tissues (n=59) were compared using the Wilcoxon rank-sum test. The expression levels of PSMA4 in LUAD tissues and normal tissues were validated by analyzing the GSE40791 and GSE10072 LUAD datasets obtained from the Gene Expression Omnibus (GEO) database. In addition, tumor and adjacent non-cancerous tissues were collected from 10 LUAD undergoing lung biopsy by fiberoptic bronchoscopy in Second Affiliated Hospital of Army Medical University from January to December 2023. The PSMA4 expression in above samples was further verified using RT-qPCR. RT-qPCR was performed to detect the expression of PSMA4 in lung cancer cells and normal lung epithelial cells. Functional enrichment analysis and immune cell infiltration analysis were conducted on the cells with high and low expression of PSMA4. Cox regression analysis and Kaplan-Meier (KM) survival analysis were used to determine the diagnostic and prognostic value of PSMA4 for LUAD, and a nomogram was constructed to predict the overall survival rate at different time points. Results The analysis of TCGA datasets, GSE40791, and GSE10072 LUAD data revealed that PSMA4 expression was significantly higher in LUAD tissues than in normal tissues (P < 0.01). RT-qPCR further confirmed that the expression of PSMA4 was obviously elevated in LUAD tissues and lung cancer cells than adjacent non-cancerous tissues and normal lung epithelial cells (P < 0.01). High PSMA4 expression could be regarded as a marker for LUAD diagnosis and poor prognosis, and was associated with reduced proportions of Tem cells, TFH cells, B cells, NK cells, Tcm cells, and mast cells in the tumor microenvironment. Conclusion PSMA4 presents significant diagnostic performance for LUAD, and is closely associated with the prognosis and immune infiltration of this malignancy.

Abstract The influence of greenhouse warming on mesoscale air-sea interactions, crucial for modulating ocean circulation and climate variability, remains largely unexplored due to the limited resolution of current climate models. Additionally, there is a lack of theoretical frameworks for assessing changes in mesoscale coupling due to warming. Here, we address these gaps by analyzing eddy-resolving high-resolution climate simulations and observations, focusing on the mesoscale thermal interaction dominated by mesoscale sea surface temperature (SST) and latent heat flux (LHF) coupling in winter. Our findings reveal a consistent increase in mesoscale SST-LHF coupling in the major western boundary current regions under warming, characterized by a heightened nonlinearity between warm and cold eddies and a more pronounced enhancement in the northern hemisphere. To understand the dynamics, we develop a theoretical framework that links mesoscale thermal coupling changes to large-scale factors, which indicates that the projected changes are collectively determined by historical background wind, SST, and the rate of SST warming. Among these factors, the large-scale SST and its warming rate are the primary drivers of hemispheric asymmetry in mesoscale coupling intensification. This study introduces a simplified approach for assessing the projected mesoscale thermal coupling changes in a warming world.

Abstract A primary driver of deep-ocean mixing is breaking of internal tides generated via interactions of barotropic tides with topography. It is important to understand how the energy conversion from barotropic to internal tides responds to global warming. Here we address this question by applying a linear model of internal tide generation to coupled global climate model simulations under a high carbon emission scenario. The energy conversion to high-mode internal tides is projected to rise by about 8% by the end of the 21st century, whereas the energy conversion to low-mode internal tides remains nearly unchanged. The intensified near-bottom stratification under global warming increases energy conversion into both low and high-mode internal tides. In contrast, the intensified depth-averaged stratification reduces the modal horizontal wavenumber of internal tides, leading to increased (decreased) energy conversion into high (low)- mode internal tides. Our findings imply stronger mixing over rough topography under global warming, which should be properly parameterized in climate models for more accurate projections of future climate changes.

BackgroundGlobally, with the popularization of mobile phones, the number of health-related mobile phone apps has skyrocketed to 259,000 in 2016. In the digital era, people are accessing health information through their fingertips. In China, there are several apps that claim to provide infant feeding and nutrition guidance. However, the quality of information in those apps has not been extensively assessed. ObjectiveWe aimed to assess the quality of Chinese infant feeding apps using comprehensive quality assessment criteria and to explore Chinese mothers’ perceptions on apps’ quality and usability. MethodsWe searched for free-to-download Chinese infant feeding apps in the iTunes and Android App Stores. We conducted a comprehensive assessment of the accountability, scientific basis, accuracy of information relevant to infant feeding, advertising policy, and functionality and carried out a preliminary screening of infant formula advertisements in the apps. In addition, we also conducted exploratory qualitative research through semistructured interviews with Chinese mothers in Shanghai to elicit their views about the quality of apps. ResultsA total of 4925 apps were screened, and 26 apps that met the selection criteria were evaluated. All 26 apps were developed by commercial entities, and the majority of them were rated poorly. The highest total score was 62.2 (out of approximately 100) and the lowest was 16.7. In the four quality domains assessed, none of them fulfilled all the accountability criteria. Three out of 26 apps provided information covering the three practices from the World Health Organization’s infant feeding recommendations. Only one app described its advertising policy in its terms of usage. The most common app functionality was a built-in social forum (19/26). Provision of a website link was the least common functionality (2/26). A total of 20 out of 26 apps promoted infant formula banner advertisements on their homepages. In addition, 12 apps included both e-commerce stores and featured infant formula advertisements. In total, 21 mothers were interviewed face-to-face. Mothers highly valued immediate access to parenting information and multifunctionality provided by apps. However, concerns regarding incredible information and commercial activities in apps, as well as the desire for information and support offered by health care professionals were expressed. ConclusionsThe findings provide valuable information on Chinese infant feeding apps. The results are concerning, particularly with the relative absence of scientific basis and credibility and the large number of commercial advertisements that are displayed. Apps do seem to be able to provide an opportunity for mothers to access health information and support; it is time for tighter controls on content and advertisements. Ongoing app research and development should focus on implementation of a standard framework, which would drive the development of high-quality apps to support healthy infant feeding through cooperation among academics, health professionals, app users, app developers, and government bodies.

The synthesis of a hapten and antigen for the preparation of a monoclonal antibody (mAb) for buprofezin is described. The recognition mechanism of hapten and buprofezin by monoclonal antibodies (mAb-19F2) is described. The effectiveness of the mAb-19F2 immunoassay technique was assessed, and the effective detection of buprofezin in tea samples was achieved through the establishment of indirect competitive enzyme-linked immunosorbent assay (ic-ELISA) and colloidal gold immunochromatography assay (GICA). The mAb-19F2 subtype was IgG1, with an IC50 of 1.8 ng/mL and a linear range (IC20-IC80) of 0.6-5.4 μg/L, and had a cross-reaction rate of less than 0.18% with 29 other pesticides (neonicotinoids and insect growth regulators). The study identified π-π stacking interactions between hapten and TYR-61 at the mAb-19F2 site and alkyl/phosphate interactions with TRP-105 and ARG-103. The ic-ELISA had an IC50 of 12.9 ng/mL in green tea and 5.65 ng/mL in black tea, with a recovery rate of 92.4%-101.0% and RSD of 2.1%-4.8%. The GICA had a limit of detection (LOD) was 500 ng/mL, with the complete disappearance of the test lines visible to the naked eye. The limit of quantitation (LOQ, IC20) was determined to be 16.8 ng/mL. Additionally, the developed GICA showed no cross-reactivity with neonicotinoid pesticides. The recovery rate of tea spiked recovered samples was 83.6%-92.2%, with an RSD of 5.3%-12.6%, and the results were consistent with the LC/MS method. This study is important for the real-time detection of buprofezin residues to ensure food safety and human health.

Background With the continuous development of society and technological innovations, the average life expectancy of human beings has gradually increased, leading to the gradual increase in the number of perimenopausal women. This trend poses a serious challenge to the management of perimenopausal health in the community. Objective To understand the health characteristics and health needs of perimenopausal women in the community, explore the relationship between the two, and provide evidence to support the development and improvement of perimenopausal health management in community health service organisations. Methods Perimenopausal women (n=260) who attended or were accompanied to the Huamu Community Health Service Centre and its subordinate stations in Pudong New Area, Shanghai, from February to March 2023 were selected as study subjects. Questionnaires were used to collect information on the health characteristics of the study subjects (related to physiological stage, social characteristics, disease status, lifestyle, and quality of life), their knowledge of menopause and attitudes toward treatment, as well as their needs for knowledge related to menopause and preventive health care for menopausal diseases. Results Fifty percent (130/260) of perimenopausal women had a current history of chronic disease, 51.9% (135/260) of perimenopausal women had a past history of chronic disease, 73.8% (192/260) of perimenopausal women had fair/poor quality of sleep, 33.5% (87/260) of perimenopausal women did little exercise. 58.5% (152/260) of perimenopausal women were completely unaware or had only heard of menopause, 41.9% (109/260) of perimenopausal women had a negative attitude towards menopause treatment, 45.0% (117/126) of perimenopausal women needed menopause-related knowledge, and 66.6% (173/260) of perimenopausal women needed preventive health care for menopausal diseases. The results of ordered multicategorical Logistic regression analyses showed that literacy, the number of menopausal symptoms in the last 3 monthss, and attitudes toward menopause treatment were the factors influencing perimenopausal women's need for menopause-related knowledge (P