TRIM37 is a primate-specific E3 ligase for Huntingtin and accounts for the striatal degeneration in Huntington's disease.

Huntington's disease (HD) is an autosomal dominant neurodegenerative disease characterized by preferential neuronal loss in the striatum. The mechanism underlying striatal selective neurodegeneration remains unclear, making it difficult to develop effective treatments for HD. In the brains of nonhuman primates, we examined the expression of Huntingtin (HTT), the gene responsible for HD. We found that HTT protein is highly expressed in striatal neurons due to its slow degradation in the striatum. We also identified tripartite motif-containing 37 (TRIM37) as a primate-specific protein that interacts with HTT and is selectively reduced in the primate striatum. TRIM37 promotes the ubiquitination and degradation of mutant HTT (mHTT) in vitro and modulates mHTT aggregation in mouse and monkey brains. Our findings suggest that nonhuman primates are crucial for understanding the mechanisms of human diseases such as HD and support TRIM37 as a potential therapeutic target for treating HD.

A comprehensive analysis of the prognostic characteristics of microRNAs in breast cancer.

Both overall survival (OS) and disease-specific survival (DSS) are significant when determining a patient's prognosis for breast cancer (BC). The effect of DSS-related microRNAs on BC susrvival, however, is not well understood. Here, we spotted differentially expressed miRNAs (DEMs) in the TCGA database of BC DSS, identified eight DSS-related miRNAs, and constructed a risk model. AUC values at 1, 3, and 5 years were 0.852, 0.861, and 0.868, respectively, indicating a risk model's excellent prognostic prediction ability. Then, we validated miRNA roles in BC OS and finally defined miR-551b as an independently prognostic miRNA in BC. According to function analysis, miR-551b is strongly linked with the emergence and spread of cancer, including protein ubiquitination, intracellular protein transport, metabolic pathways, and cancer pathways. Moreover, we confirmed the low expression of miR-551b in BC tissue and cells. After miR-551b inhibition or overexpression, cell function was either dramatically increased or diminished, respectively, indicating that miR-551b could regulate BC proliferation, invasion, and migration. In conclusion, we thoroughly clarified BC-related miRNAs on DSS and OS and verified miR-551b as a crucial regulator in the development and prognosis of cancer. These results can offer fresh ideas for BC therapy.

The prognostic and antitumor roles of key genes of ferroptosis in liver hepatocellular cancer and stomach adenocarcinoma.

BACKGROUND: Liver hepatocellular cancer (LIHC) and stomach adenocarcinoma (STAD) are common malignancies with high lethal ratios worldwide. Great progress has been achieved by using diverse therapeutic strategies; however, these diseases still have an unfavourable prognosis. Ferroptosis inducer drugs, unlike apoptosis-related drugs, can overcome the resistance to cancer therapy caused by traditional chemicals. However, the relationship between overall survival (OS) and ferroptosis-related genes, as well as the mechanisms involved, are largely unclear. METHODS: The expression levels of AIFM2, GPX4, ACSL4, FTH1, NOS1, and PTGS2 in LIHC and STAD were obtained from UALCAN. The correlations of OS with these gene expression levels were obtained using the Kaplan-Meier Plotter database. The OS associated with genetic mutations of those genes compared to that of unchanged genes was analysed using the TIMER website. GO and KEGG enrichment analyses of ferroptosis-related genes and their coexpressed genes in LIHC and STAD were conducted using the STRING and DAVID databases. The relationship of PTGS2 and ACSL4 to immune cell infiltration was analysed using the TIMER website. The viability and GPX5 expression levels in LIHC cells treated with RSL3 and As2O3 were detected by MTT methods and western blotting, respectively. RESULTS: Our results showed that GPX4, FTH1 and AIFM2 were overexpressed in LIHC and STAD. High levels of GPX4, FTH1 and AIFM2 were prominently correlated with better prognosis in LIHC. However, GPX and FTH1 in STAD did not show significant correlations with OS. AIFM2 in STAD had the opposite trend with OS compared with that in LIHC. Moreover, a high mutation rate of these genes (35.74%) was also observed in LIHC patients, and genetic mutation of these genes was correlated with shorter OS. In contrast, the genetic mutation of these genes did not change OS in STAD. Enrichment analysis showed that the respiratory electron transport chain, cell chemotaxis and T-cell migration were related to ferroptosis. ASCL4 and PTGS2 coexpressed with cytokines associated with immune cell infiltration. Compared to RSL3 or As2O3 alone, As2O3 plus RSL3 significantly inhibited the growth of Huh7 cells. GPX4 was downregulated to an undetectable level when in combination with RSL3. CONCLUSIONS: Our results indicated that ferroptosis-related genes might play an important role in LIHC and STAD and might be risk factors for overall survival in LIHC and STAD.

Changes in gut microbiota and cytokines following laparoscopic sleeve gastrectomy are associated with cognitive function improvement.

Purpose: Variations of cytokines and gut microbiota diversity with improved cognitive function in patients with obesity following bariatric surgery were poorly understood. The aim of this study was to testify the relationship among gut microbiota, cytokines and cognitive function in patients with obesity before and after laparoscopic sleeve gastrectomy (LSG). Methods: Forty patients were enrolled in this study. Demographics, and serum and stool specimens were collected from all patients before and 3 months after LSG. The Montreal Cognitive Assessment (MoCA) scale, as well as assessment of immediate and delayed memory were used to evaluate self-perceived cognitive improvement after LSG. Results: LSG resulted in significant weight loss and improvement in cognitive functions, as measured by questionnaires. Bariatric surgery tended to increase gut microbiota relative abundance and diversity. The intestinal flora increased in the proportion of Bacteroidetes and Fusobacteria phyla, and decreased in the proportion of Firmicutes, Proteobacteria, and Actinobacteria phyla after LSG. Plasma IL-1ß and TNF-α levels were significantly decreased following LSG, while IL-4 was significantly increased. MoCA test scores were significant correlated with IL-4, TNF-α and IL-1ß. In addition, Firmicutes had a positive correlation with TNF-α, while Fuscobacteria had a negative correlation with IL-1ß. Bacteroidetes was negatively correlated with IL-4. Conclusion: Changes in gut microbiota were positive relationship with cognitive function improvement following LSG. Inflammation cytokines maybe played as a mediator between gut microbiota and cognitive function through gut-microbiota-brain axis.

Systemic Chemotherapy With or Without Hepatic Arterial Infusion Chemotherapy for Liver Metastases From Pancreatic Cancer: A Propensity Score Matching Analysis.

BACKGROUND: The significance of systemic chemotherapy (SCT) combined with hepatic arterial infusion (HAI) chemotherapy in the treatment of pancreatic ductal adenocarcinoma with liver metastases (PACLM) remains unclear. Based on previous studies, this single-center propensity score matching (PSM) study aimed to explore the efficacy of SCT with or without HAI for PACLM. PATIENT AND METHODS: The PSM method was used to screen 661 cases of PACLM who received SCT at Tianjin Medical University Cancer Institute and Hospital from 2001 to 2020. According to the 1:6 ratio with PSM, 385 patients were divided into the SCT+HAI group (n = 55) and the SCT group (n = 330). After a median follow-up of 49 (range 7-153) months, overall survival (OS) and survival-related prognostic factors were analyzed. RESULTS: The main baseline characteristics of the SCT+HAI group and the SCT alone group were matched appropriately (P > .05). After PSM, the median OS for patients in the 2 groups was 10.6 and 7.6 months, respectively (P = .02). Multivariate analysis revealed that peritoneal metastases (P = .03), CA199 ≥ 500U/mL (P = .03), and lactate dehydrogenase (LDH) ≥ 250U/L (P = .03) were prognostic factors of poor survival, modern SCT plus HAI (P = .04) was a protective factor. CONCLUSION: Our findings indicated that adequate cycles of SCT+HAI result in better survival than SCT alone in patients with PACLM. Patients with peritoneal metastases, markedly elevated CA19-9 and LDH have a poorer prognosis. The conclusion has yet to be validated in randomized controlled clinical trials.

Indicator-Free Argentometric Titration for Distance-Based Detection of Chloride Using Microfluidic Paper-Based Analytical Devices.

We described an indicator-free argentometric titration strategy using a microfluidic paper-based analytical device. This strategy was based on the formation of insoluble silver salts by reactions occurring between analytes and titrant (Ag+) on a paper channel. After the insoluble silver salts were formed and precipitated on the channel, the paper substrate modified with the surplus titrant on the channel turned reddish-brown by exposure of the devices to a simple and cheap UV light source for 5 min, generating a colored band on the channel. Distance-based detection of chloride was achieved by measuring the length of the colored band with a detection limit of 1.7 mg L-1 Cl-. This method was used to detect chlorides in tap water, with an analytical result (10.1 ± 1.2 mg L-1) agreeing well with that obtained by a classical conventional precipitation titration (9.8 mg L-1), which was based on the measurement of the consumed volume of titrant. This paper-based precipitation titration method is free of skilled personnel and has advantages of low reagent/sample consumption, disposability, portability, and simple operation over the conventional precipitation titration. More importantly, being free of any indicator, this method may be used to detect more species than the conventional precipitation titrations, which are limited by the indicator, for example, CO3 2- and SO4 2-, which could form insoluble silver salts in aqueous liquids. Additionally, comparing with most of those paper-based titrimetry reported previously, this presented precipitation titration is free of any indicator or ion selective electrode to detect the end point of titration.

Instrument-free detection of polyphenols with a thread-based analytical device.

We described an instrument-free method for quantitative analysis of the total content of tea polyphenols by measurement of the length of a coloured band. Polyphenols react with ferrous ions to form a colourless ferrous-polyphenols complex on cotton threads, which could be adsorbed on the threads. The complex was then oxidized to form a blue-black ferric-polyphenols complex, generating a blue-black band on the cotton thread. The length of this blue-black band was then measured to detect the total content of polyphenols. The advantages of this method include low cost, rapid analysis, low consumption, easy fabrication and operation. Furthermore, the digital instrument (scanner or camera) as well as the image processing software are not required. This proposed method was used to detect polyphenols in tea leaf extracts with an analytical result agreeing well with that obtained by a standard method, which demonstrates its potential in monitoring of tea leaf quality, especially in resource-limited regions and settings.

Lifting motion simulation using a hybrid approach.

In this study, a hybrid dynamic model for lifting motion simulation is presented. The human body is represented by a two-dimensional (2D) five-segment model. The lifting motions are predicted by solving a nonlinear optimisation problem, the objective function of which is defined based on a minimal-effort performance criterion. In the optimisation procedure, the joint angular velocities are bounded by time-functional constraints that are determined by actual motions. Symmetric lifting motions performed by younger and older adults under varied task conditions were simulated. Comparisons between the simulation results and actual motion data were made for model evaluation. The results showed that the mean and median joint angle errors were less than 10°, which suggests the proposed model is able to accurately simulate 2D lifting motions. The proposed model is also comparable with the existing motion simulation models in terms of the prediction accuracy. Strengths and limitations of this hybrid model are discussed. Practitioner Summary: Human motion simulation is a useful tool in assessing the risks of occupational injuries. Lifting motions are associated with low-back pain. A hybrid model for lifting motion simulation was constructed. The model was able to accurately simulate 2D lifting motions in varied task scenarios for younger and older subjects.

Effects of age and its interaction with task parameters on lifting biomechanics.

This study investigated the age-related differences in lifting biomechanics. Eleven younger and 12 older participants were instructed to perform symmetric lifting tasks defined by different combinations of destination heights and load magnitudes. Lifting biomechanics was assessed. It was found that the trunk flexion in the starting posture was 32% lower and the peak trunk extension velocity was 46% lower in older participants compared with those in younger ones, indicating that older adults tended to use safer lifting strategies than did younger adults. Based on these findings, we recommend that physical exercise programmes may be a more effective ergonomic intervention for reducing the risks of low back pain (LBP) in lifting among older workers, compared with instructions of safe lifting strategies. As for younger workers, instructions of safe lifting strategies would be effective in LBP risk reduction.