HRD1 promotes non-small cell lung carcinoma metastasis by blocking autophagy-mediated MIEN1 degradation.

Dysregulation of autophagy has been implicated in the development of many diseases, including cancer. Here, we revealed a novel function of the E3 ubiquitin ligase HRD1 in non-small cell lung carcinoma (NSCLC) metastasis by regulating autophagy. Mechanistically, HRD1 inhibits autophagy by promoting ATG3 ubiquitination and degradation. Additionally, a pro-migratory and invasive factor, MIEN1 (migration and invasion enhancer 1), was found to be autophagically degraded upon HRD1 deficiency. Importantly, expression of both HRD1 and MIEN1 are upregulated and positively correlated in lung tumors. Based on these results, we proposed a novel mechanism of HRD1 function that the degradation of ATG3 protein by HRD1 leads to autophagy inhibition and MIEN1 release, thus promoting NSCLC metastasis. Therefore, our findings provided new insights into the role of HRD1 in NSCLC metastasis and new therapeutic targets for lung cancer treatment.

Stabilization of SETD3 by deubiquitinase USP27 enhances cell proliferation and hepatocellular carcinoma progression.

The histone methyltransferase SETD3 plays critical roles in various biological events, and its dysregulation is often associated with human diseases including cancer. However, the underlying regulatory mechanism remains elusive. Here, we reported that ubiquitin-specific peptidase 27 (USP27) promotes tumor cell growth by specifically interacting with SETD3, negatively regulating its ubiquitination, and enhancing its stability. Inhibition of USP27 expression led to the downregulation of SETD3 protein level, the blockade of the cell proliferation and tumorigenesis of hepatocellular carcinoma (HCC) cells. In addition, we found that USP27 and SETD3 expression is positively correlated in HCC tissues. Notably, higher expression of USP27 and SETD3 predicts a worse survival in HCC patients. Collectively, these data elucidated that a USP27-dependent mechanism controls SETD3 protein levels and facilitates its oncogenic role in liver tumorigenesis.

Long-term care needs and hospitalization costs with long-term care insurance: a mixed-sectional study.

Background: With the rapid aging of the population, the health needs of the older adult have increased significantly, resulting in the frequent occurrence of the "social hospitalization" problem, which has led to a rapid increase in hospitalization costs. This study investigates whether the "social hospitalization problem" arising from the long-term care needs can be solved through the implementation of long-term care insurance, thereby improving the overall health of the older adults and controlling the unreasonable increase in hospitalization costs. Methods: The entropy theory was used as a conceptual model, based on data from the China Health and Retirement Longitudinal Study (CHARLS) in 2015 and 2018. The least-squares method was used to examine the relationship between long-term care needs and hospitalization costs, and the role that long-term care insurance implementation plays in its path of influence. Results: The results of this study indicated that long-term care needs would increase hospitalization cost, which remained stable after a series of tests, such as replacing the core explanatory variables and introducing fixed effects. Through the intermediary effect test and mediated adjustment effect test, we found the action path of long-term care needs on hospitalization costs. Long-term care needs increases hospitalization costs through more hospitalizations. Long-term care insurance reduces hospitalization costs. Its specific action path makes long-term care insurance reduce hospitalization costs through a negative adjustment of the number of hospitalizations. Conclusion: To achieve fair and sustainable development of long-term care insurance, the following points should be achieved: First, long-term care insurance should consider the prevention in advance and expand the scope of participation and coverage; Second, long-term care insurance should consider the control in the event and set moderate levels of treatment payments; Third, long-term care insurance should consider post-supervision and explore appropriate payment methods.

Proteomics coupled transcriptomics reveals Slc34a1 and Slc34a3 downregulation as potential features of nephrotoxin-induced acute kidney injury.

Acute kidney injury (AKI) stands as a prevalent and economically burdensome condition worldwide, yet its complex molecular mechanisms remain incompletely understood. To address this gap, our study employs a multifaceted approach, combining mass spectrometry and RNA sequencing technologies, to elucidate the intricate molecular landscape underlying nephrotoxin-induced AKI in mice by cisplatin- and LPS-induced. By examining the protein and RNA expression profiles, we aimed to uncover novel insights into the pathogenesis of AKI and identify potential diagnostic and therapeutic targets. Our results demonstrate significant down-regulation of Slc34a1 and Slc34a3, shedding light on their crucial roles in AKI pathology and highlighting their promise as actionable targets for diagnosis and treatment. This comprehensive analysis not only enhances our understanding of AKI pathophysiology but also offers valuable avenues for the development of targeted interventions to mitigate its clinical impact. SIGNIFICANCE: Nephrotoxicity acute kidney injury (AKI) is a common clinical condition whose pathogenesis is the process by which some drugs, chemicals or other factors cause damage to the kidneys, resulting in impaired kidney function. Although it has been proved that different nephrotoxic substances can affect the kidney through different pathways, whether they have a commonality has not been registered. Here, we combined transcriptomics and proteomics to study the molecular mechanism of LPS and cisplatin-induced nephrotoxic acute kidney injury finding that the down-regulation of Slc34a1 and Slc34a3 may be a critical link in nephrotoxic acute kidney injury, which can be used as a marker for its early diagnosis.

Single-cell Clonal Tracing of Glandular and Circulating T cells identifies a population of CD9+CD8+T cells in primary Sjogren's Syndrome.

Primary Sjogren's syndrome (pSS) is a complex chronic autoimmune disease in which local tissue damage in exocrine glands are combined with broader systemic involvement across the body in tissues including the skin. These combined manifestations negatively impact patient health and quality of life. While studies have previously reported differences in immune cell composition in the peripheral blood of pSS patients relative to healthy controls, a detailed immune cell landscape of the damaged exocrine glands of these patients remains lacking. Through single-cell transcriptomics and repertoire sequencing of immune cells in paired peripheral blood samples and salivary gland biopsies, we present here a preliminary picture of adaptive immune response in pSS. We characterize a number of points of divergence between circulating and glandular immune responses that have been hitherto underappreciated, and identify a novel population of CD8+CD9+ cells with tissue-residential properties that are highly enriched in the salivary glands of pSS patients. Through comparative analyses with other sequencing data, we also observe a potential connection between these cells and the tissue-resident memory cells found in cutaneous vasculitis lesions. Together, these results indicate a potential role for CD8+CD9+ cells in mediating glandular and systemic effects associated with pSS and other autoimmune disorders.

Effects of social assistance on self-rated health.

Based on the China Health and Retirement Longitudinal Study (CHARLS) data in 2018, medical assistance and life assistance have significant negative influences on self-rated health, found via an empirical analysis based on the Oprobit model. Such negative influences are robust based on the substitution of explained variables and propensity score matching. It can be found from a heterogeneity analysis that the negative influences of medical assistance on self-rated health are more significant in urban residents and residents in Central China and East China. Meanwhile, negative influences of life assistance on self-rated health are more significant in urban residents, and residents in Central China, East China, and Northeast China. This study provides empirical evidence to improve the health of residents by using medical assistance and life assistance accurately and offers important policy enlightenments to formulate appropriate social assistance policies.