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Ubiquitination is vital for multiple cellular processes via dynamic modulation of proteins related to cell growth, proliferation, and survival. Of the ubiquitination system components, E3 ubiquitin ligases and deubiquitinases have the most prominent roles in modulating tumor metastasis. This review will briefly summarize the observations and underlying mechanisms of multiple E3 ubiquitin ligases and deubiquitinases to regulate tumor metastasis. Further, we will discuss the relationship and importance between ubiquitination components and tumor progression.

The E3 ligase S-phase kinase-associated protein 2(Skp2) is overexpressed in human cancers and correlated with poor prognosis, but its contributions to tumorigenesis and chemoresistance in nasopharyngeal carcinoma (NPC) are not evident. Herein we show that Skp2 is highly expressed in NPC tumor tissues and cell lines. Knockdown of Skp2 suppresses tumor cell growth, colony formation, glycolysis, and in vivo tumor growth. Skp2 promotes Akt K63-mediated ubiquitination and activation, which is required for EGF-induced Akt mitochondrial localization. Importantly, K63-linked ubiquitination enhances the interaction between Akt and HK2 and eventually increases HK2 phosphorylation on Thr473 and mitochondrial localization. Overexpression of Skp2 impaired the intrinsic apoptotic pathway and confers cisplatin resistance. Moreover, ectopic expression of Myr-Akt1 or phosphomimetic HK2-T473D rescued cisplatin-induced tumor suppression in Skp2 knockdown stable cells. Also, depletion of Akt ubiquitination enhances the antitumor efficacy of cisplatin in vitro and in vivo. Finally, we demonstrated that Skp2 is positively correlated with p-Akt and HK2 in NPC tumor tissues. This study highlights the clinical value of Skp2 targeting in NPC treatment.

Silent information regulator 1 (SIRT1) is a nicotinamide adenine dinucleotide (NAD +)-dependent protein deacetylase that exerts biological effects through nucleoplasmic transfer. Recent studies have highlighted that SIRT1 deacetylates protein substrates to exert its neuroprotective effects, including decreased oxidative stress and inflammatory, increases autophagy, increases levels of nerve growth factors (correlated with behavioral changes), and maintains neural integrity (affects neuronal development and function) in aging or neurological disorder. In this review, we highlight the molecular mechanisms underlying the protective role of SIRT1 in modulating neurodegeneration, focusing on protein homeostasis, aging-related signaling pathways, neurogenesis, and synaptic plasticity. Meanwhile, the potential of targeting SIRT1 to block the occurrence and progression of neurodegenerative diseases is also discussed. Taken together, this review provides an up-to-date evaluation of our current understanding of the neuroprotective mechanisms of SIRT1 and also be involved in the potential therapeutic opportunities of AD and related neurodegenerative diseases.

Internet hospitals, which refer to service platforms that integrate consultation, prescription, payment, and drug delivery based on hospital entities, have been developing at a rapid pace in China since 2014. However, assessments regarding their service quality and patient satisfaction have not been well developed. There is an urgent need to comprehensively evaluate and improve the service quality of internet hospitals. This study aims to investigate the current status of patients' use of internet hospitals, as well as familiarity and willingness to use internet hospitals, to evaluate patients' expected and perceived service qualities of internet hospitals using the Chinese version of the Service Quality Questionnaire (SERVQUAL-C) with a national representative sample, and to explore the association between service quality of internet hospitals and patients' overall satisfaction toward associated medical platforms. This cross-sectional survey was conducted through face-to-face or digital interviews from June to September 2022. A total of 1481 outpatient participants (635 men and 846 women; mean age 33.22, SD 13.22). Participants reported their use of internet hospitals, and then rated their expectations and perceptions of service quality toward internet hospitals via the SERVQUAL-C, along with their demographic information. Among the surveyed participants, 51.2% (n=758) of participants had used internet hospital service or services. Use varied across age, education level, and annual income. Although the majority of them (n=826, 55.8%) did not know internet hospital services well, 68.1% (n=1009) of participants expressed the willingness to adopt this service. Service quality evaluation revealed that the perceived service quality did not match with the expectation, especially the responsiveness dimension. Important-performance analysis results further alerted that reliable diagnosis, prompt response, clear feedback pathway, and active feedback handling were typically the services awaiting substantial improvement. More importantly, multiple linear regressions revealed that familiarity and willingness to use internet hospital services were significant predictors of satisfaction, above and over tangibles, reliability, and empathy service perspectives, and demographic characteristics such as gender, age, education level, and annual income. In the future, internet hospitals should focus more on how to narrow the gaps between the expected and perceived service quality. Promotion of internet hospitals should also be facilitated to increase patients' familiarity with and willingness to use these services.

Tumor-associated macrophages (TAMs), the most abundant inflammatory cell group in the tumor microenvironment, play an essential role in tumor immune regulation. The infiltration degree of TAMs in the tumor microenvironment is closely related to tumor growth and metastasis, and TAMs have become a promising target in tumor immunotherapy. Molecular imaging is a new interdisciplinary subject that combines medical imaging technology with molecular biology, nuclear medicine, radiation medicine, and computer science. The latest progress in molecular imaging allows the biological processes of cells to be visualized in vivo, which makes it possible to better understand the density and distribution of macrophages in the tumor microenvironment. This review mainly discusses the application of targeting TAM in tumor immunotherapy and the imaging characteristics and progress of targeting TAM molecular probes using various imaging techniques.

In 2016 Delong et al. discovered a new type of neoepitope formed by the fusion of two unrelated peptide fragments. Remarkably these neoepitopes, called hybrid insulin peptides, or HIPs, are recognized by pathogenic CD4 + T cells in the NOD mouse and human pancreatic islet-infiltrating T cells in people with type 1 diabetes. Current data implicates CD4 + T-cell responses to HIPs in the immune pathogenesis of human T1D. Because of their role in the immune pathogenesis of human T1D it is important to identify new HIPs that are recognized by CD4 + T cells in people at risk of, or with, T1D. A detailed knowledge of T1D-associated HIPs will allow HIPs to be used in assays to monitor changes in T cell mediated beta-cell autoimmunity. They will also provide new targets for antigen-specific therapies for T1D. However, because HIPs are formed by the fusion of two unrelated peptides there are an enormous number of potential HIPs which makes it technically challenging to identify them. Here we review the discovery of HIPs, how they form and discuss approaches to identifying new HIPs relevant to the immune pathogenesis of human type 1 diabetes.

Background Concurrent hexavalent chromium [Cr(VI)] and chlorfenapyr contamination in aquatic environments poses risks to environmental organisms. A parental zebrafish ( Danio rerio ) exposure model with multi-omics analyses was used to elucidate molecular and transgenerational effects. Results Combined exposure decreased intestinal tight junction transcription ( zo-1 , and occludin ), caused morphological damage, and activated pro-inflammatory cytokines ( il-1β , il-6 , il-8 , and TNF-α ). 16S rRNA sequencing revealed reduced butyrate-producing bacteria (e.g., Coprococcus ), while untargeted metabolomics showed declines in phospholipid precursors (choline, and glycerophosphocholine), implicating disrupted gut barrier metabolism. Hepatic transcriptomics identified downregulation of oxidative phosphorylation components ( atp5l , atp5mc3b , atp5po , and ndufs7 ) and antioxidant enzymes ( gpx , and mn-sod ), correlating with decreased ATP, mitochondrial membrane potential, and increased apoptosis. F₁ offspring exhibited aberrations in gene transcriptions associated with oxidative phosphorylation and inflammation, suggesting the presence of intergenerational toxicity. Conclusions These results highlighted the gut-liver axis and mitochondrial function as targets for molecular biomarkers and inform eco-safety regulation addressing chemical mixture hazards.

Carbon isotope logging technology can obtain timely and accurate hydrocarbon fluid and reservoir geological information and has great application potential in oil–gas body property analysis, the comprehensive study of source rocks, and fault-sealing evaluation. Since 2014, real-time methane isotope logging technology has been applied in the western South China Sea. Based on the on-site, real-time, continuous, and accurate detection of methane carbon isotopes, combined with the rapid comprehensive analysis and evaluation of logging gas measurement data, the application effect in ultra-high-temperature and high-pressure wells in the western South China Sea has been remarkable. Taking the Ledong 10 Area of Yinggehai Basin as an example, real-time carbon isotope logging data can be used to quickly identify gas origins, source rock maturity, and gas source type and help judge the sealing quality of overburdened mudstone caps. This knowledge can serve as a reference for ascertaining the popularity of isotope-logging technology in other areas.

Some anthropogenic pollutants, such as heavy metals and nanoparticles (NPs), are widely distributed and a major threat to environmental safety and public health. In particular, lead (Pb), cadmium (Cd), chromium (Cr), arsenic (As), and mercury (Hg) have systemic toxicity even at extremely low concentrations, so they are listed as priority metals in relation to their significant public health burden. Aluminum (Al) is also toxic to multiple organs and is linked to Alzheimer’s disease. As the utilization of many metal nanoparticles (MNPs) gradually gain traction in industrial and medical applications, they are increasingly being investigated to address potential toxicity by impairing certain biological barriers. The dominant toxic mechanism of these metals and MNPs is the induction of oxidative stress, which subsequently triggers lipid peroxidation, protein modification, and DNA damage. Notably, a growing body of research has revealed the linkage between dysregulated autophagy and some diseases, including neurodegenerative diseases and cancers. Among them, some metals or metal mixtures can act as environmental stimuli and disturb basal autophagic activity, which has an underlying adverse health effect. Some studies also revealed that specific autophagy inhibitors or activators could modify the abnormal autophagic flux attributed to continuous exposure to metals. In this review, we have gathered recent data about the contribution of the autophagy/mitophagy mediated toxic effects and focused on the involvement of some key regulatory factors of autophagic signaling during exposure to selected metals, metal mixtures, as well as MNPs in the real world. Besides this, we summarized the potential significance of interactions between autophagy and excessive reactive oxygen species (ROS)-mediated oxidative damage in the regulation of cell survival response to metals/NPs. A critical view is given on the application of autophagy activators/inhibitors to modulate the systematic toxicity of various metals/MNPs.

The addition of lipophilic opioids to local anesthetics for spinal anesthesia has become a widely used strategy for cesarean anesthesia. A meta-analysis to quantify the benefits and risks of combining sufentanil with bupivacaine for patients undergoing cesarean delivery was conducted. A comprehensive literature search without language or date limitation was performed to identify clinical trials that compared the addition of sufentanil to bupivacaine with bupivacaine alone for spinal anesthesia in healthy parturients choosing cesarean delivery. The Q and I2 tests were used to assess heterogeneity of the data. Data from each trial were combined using relative ratios (RRs) for dichotomous data or weighted mean differences (WMDs) for continuous data and corresponding 95% confidence intervals (95% CIs) for each trial. Sensitivity analysis was conducted by removing one study a time to assess the quality and consistency of the results. Begg's funnel plots and Egger's linear regression test were used to detect any publication bias. This study included 9 trials containing 578 patients in the final meta-analysis. Sufentanil addition provided a better analgesia quality with less breakthrough pain during surgery than bupivacaine alone (RR = 0.10, 95% CI 0.06 to 0.18, P < 0.001). Sensory block onset time was shorter and first analgesic request time was longer in sufentanil added group compared with the bupivacaine-alone group (WMD = -1.0 min, 95% CI -1.5 to -0.58, P < 0.001 and WMD = 133 min, 95% CI 75 to 213, P < 192, respectively). There was no significant difference in the risk of hypotension and vomiting between these two groups. But pruritus was more frequentely reported in the group with sufentanil added (RR = 7.63, 95% CI 3.85 to 15.12, P < 0.001). Bupivacaine and sufentanil combination is superior to that of bupivacaine alone for spinal anesthesia for cesarean delivery in analgesia quality. Women receiving the combined two drugs had less breakthrough pain, shorter sensory block onset time, and longer first analgesic request time. However, the addition of sufentanil to bupivacaine increased the incidence of pruritus.