DNA-DISK: Automated end-to-end data storage via enzymatic single-nucleotide DNA synthesis and sequencing on digital microfluidics.

In the age of information explosion, the exponential growth of digital data far exceeds the capacity of current mainstream storage media. DNA is emerging as a promising alternative due to its higher storage density, longer retention time, and lower power consumption. To date, commercially mature DNA synthesis and sequencing technologies allow for writing and reading of information on DNA with customization and convenience at the research level. However, under the disconnected and nonspecialized mode, DNA data storage encounters practical challenges, including susceptibility to errors, long storage latency, resource-intensive requirements, and elevated information security risks. Herein, we introduce a platform named DNA-DISK that seamlessly streamlined DNA synthesis, storage, and sequencing on digital microfluidics coupled with a tabletop device for automated end-to-end information storage. The single-nucleotide enzymatic DNA synthesis with biocapping strategy is utilized, offering an ecofriendly and cost-effective approach for data writing. A DNA encapsulation using thermo-responsive agarose is developed for on-chip solidification, not only eliminating data clutter but also preventing DNA degradation. Pyrosequencing is employed for in situ and accurate data reading. As a proof of concept, DNA-DISK successfully stored and retrieved a musical sheet file (228 bits) with lower write-to-read latency (4.4 min of latency per bit) as well as superior automation compared to other platforms, demonstrating its potential to evolve into a DNA Hard Disk Drive in the future.

Crucial effect of ovomucin on alkali-induced egg white gel formation: Properties, structure and facilitation mechanism.

Alkali-induced preserved egg gel formation is a dynamic process that involves complex protein changes. Ovomucin (OVM) is closely associated with the gel properties of egg white. In this study, the effect of OVM in alkali-induced egg white gel (AEWG) formation was investigated. The results suggested that OVM reduced the gel formation time by 15 %. The mechanical properties of the fully formed gel were also improved by OVM. Specifically, OVM increased the storage modulus (G') of the gel by 1.5-fold, while the hardness significantly increased from 78.90 ± 4.24 g to 99.80 ± 9.23 g. Low-field nuclear magnetic resonance (LF-NMR) demonstrated that OVM significantly shortened T23 relaxation time and reduced the water mobility, thus increasing the water holding capacity (WHC). Meanwhile, the presence of OVM resulted in a more homogeneous and denser microscopic morphology of the gel. Selective solubility experiments revealed that disulfide bonds are the primary force in gel formation. OVM promoted the formation of more disulfide bonds, which increased the strength and stability of the gel network. Overall, this research proved OVM plays a critical role in the performance improvement of AEWG, which provides a new insight into the quality control of preserved egg and protein gel foods.

Terahertz Spectra of Mannitol and Erythritol: A Joint Experimental and Computational Study.

Sugar substitutes, which generally refer to a class of food additives, mostly have vibration frequencies within the terahertz (THz) band. Therefore, THz technology can be used to analyze their molecular properties. To understand the characteristics of sugar substitutes, this study selected mannitol and erythritol as representatives. Firstly, PXRD and Raman techniques were used to determine the crystal structure and purity of mannitol and erythritol. Then, the THz time-domain spectroscopy (THz-TDS) system was employed to measure the spectral properties of the two sugar substitutes. Additionally, density functional theory (DFT) was utilized to simulate the crystal configurations of mannitol and erythritol. The experimental results showed good agreement with the simulation results. Finally, microfluidic chip technology was used to measure the THz spectroscopic properties of the two sugar substitutes in solution. A comparison was made between their solid state and aqueous solution state, revealing a strong correlation between the THz spectra of the two sugar substitutes in both states. Additionally, it was found that the THz spectrum of a substance in solution is related to its concentration. This study provides a reference for the analysis of sugar substitutes.

Performance of GPT-4 on Chinese Nursing Examination: Potentials for AI-Assisted Nursing Education Using Large Language Models.

BACKGROUND: The performance of GPT-4 in nursing examinations within the Chinese context has not yet been thoroughly evaluated. OBJECTIVE: To assess the performance of GPT-4 on multiple-choice and open-ended questions derived from nursing examinations in the Chinese context. METHODS: The data sets of the Chinese National Nursing Licensure Examination spanning 2021 to 2023 were used to evaluate the accuracy of GPT-4 in multiple-choice questions. The performance of GPT-4 on open-ended questions was examined using 18 case-based questions. RESULTS: For multiple-choice questions, GPT-4 achieved an accuracy of 71.0% (511/720). For open-ended questions, the responses were evaluated for cosine similarity, logical consistency, and information quality, all of which were found to be at a moderate level. CONCLUSION: GPT-4 performed well at addressing queries on basic knowledge. However, it has notable limitations in answering open-ended questions. Nursing educators should weigh the benefits and challenges of GPT-4 for integration into nursing education.

Effectiveness of eHealth Interventions in Improving Medication Adherence Among Patients With Cardiovascular Disease: Systematic Review and Meta-Analysis.

BACKGROUND: Nonadherence to medication among patients with cardiovascular diseases undermines the desired therapeutic outcomes. eHealth interventions emerge as promising strategies to effectively tackle this issue. OBJECTIVE: The aim of this study was to conduct a network meta-analysis (NMA) to compare and rank the efficacy of various eHealth interventions in improving medication adherence among patients with cardiovascular diseases (CVDs). METHODS: A systematic search strategy was conducted in PubMed, Embase, Web of Science, Cochrane, China National Knowledge Infrastructure Library (CNKI), China Science and Technology Journal Database (Weipu), and WanFang databases to search for randomized controlled trials (RCTs) published from their inception on January 15, 2024. We carried out a frequentist NMA to compare the efficacy of various eHealth interventions. The quality of the literature was assessed using the risk of bias tool from the Cochrane Handbook (version 2.0), and extracted data were analyzed using Stata16.0 (StataCorp LLC) and RevMan5.4 software (Cochrane Collaboration). The certainty of evidence was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach. RESULTS: A total of 21 RCTs involving 3904 patients were enrolled. The NMA revealed that combined interventions (standardized mean difference [SMD] 0.89, 95% CI 0.22-1.57), telephone support (SMD 0.68, 95% CI 0.02-1.33), telemonitoring interventions (SMD 0.70, 95% CI 0.02-1.39), and mobile phone app interventions (SMD 0.65, 95% CI 0.01-1.30) were statistically superior to usual care. However, SMS compared to usual care showed no statistical difference. Notably, the combined intervention, with a surface under the cumulative ranking curve of 79.3%, appeared to be the most effective option for patients with CVDs. Regarding systolic blood pressure and diastolic blood pressure outcomes, the combined intervention also had the highest probability of being the best intervention. CONCLUSIONS: The research indicates that the combined intervention (SMS text messaging and telephone support) has the greatest likelihood of being the most effective eHealth intervention to improve medication adherence in patients with CVDs, followed by telemonitoring, telephone support, and app interventions. The results of these network meta-analyses can provide crucial evidence-based support for health care providers to enhance patients' medication adherence. Given the differences in the design and implementation of eHealth interventions, further large-scale, well-designed multicenter trials are needed. TRIAL REGISTRATION: INPLASY 2023120063; https://inplasy.com/inplasy-2023-12-0063/.

Temperature modification of air pollutants and their synergistic effects on respiratory diseases in a semi-arid city in Northwest China.

Air pollutants and temperature are significant threats to public health, and the complex linkages between the environmental factors and their interactions harm respiratory diseases. This study is aimed to analyze the impact of air pollutants and meteorological factors on respiratory diseases and their synergistic effects in Dingxi, a city in northwestern China, from 2018 to 2020 using a generalized additive model (GAM). Relative risk (RR) was employed to quantitatively evaluate the temperature modification on the short-term effects of PM2.5 and O3 and the synergistic effects of air pollutants (PM2.5 and O3) and meteorological elements (temperature and relative humidity) on respiratory diseases. The results indicated that the RRs per inter-quatile range (IQR) rise in PM2.5 and O3 concentrations were (1.066, 95% CI: 1.009-1.127, lag2) and (1.037, 95% CI: 0.975-1.102, lag4) for respiratory diseases, respectively. Temperature stratification suggests that the influence of PM2.5 on respiratory diseases was significantly enhanced at low and moderate temperatures, and the risk of respiratory diseases caused by O3 was significantly increased at high temperatures. The synergy analysis demonstrated significant a synergistic effect of PM2.5 with low temperature and high relative humidity and an antagonistic effect of high relative humidity and O3 on respiratory diseases. The findings would provide a scientific basis for the impact of pollutants on respiratory diseases in Northwest China.

Trehalose and its dihydrate: terahertz insights from solid to solution states.

Carbohydrates are pivotal biomolecules in biochemistry; this study employs terahertz time-domain spectroscopy (THz-TDS) to investigate the spectral characteristics of trehalose and its hydrate across the 0.1 to 2.2 THz frequency range. Notable differences in spectra between the two compounds were observed. Density Functional Theory (DFT) simulations of the crystal structure were conducted to elucidate this phenomenon. The consistency between experimental results and simulations substantiates the reliability of the experimental findings. Additionally, the spectral characteristics of these carbohydrates in solution were examined using microfluidic chip technology. This approach facilitates a comprehensive comparison of their behaviors in both solid and solution states.

Characterization of air pollution and associated health risks in Gansu Province, China from 2015 to 2022.

Air pollution poses a major threat to both the environment and public health. The air quality index (AQI), aggregate AQI, new health risk-based air quality index (NHAQI), and NHAQI-WHO were employed to quantitatively evaluate the characterization of air pollution and the associated health risk in Gansu Province before (P-I) and after (P-II) COVID-19 pandemic. The results indicated that AQI system undervalued the comprehensive health risk impact of the six criteria pollutants compared with the other three indices. The stringent lockdown measures contributed to a considerable reduction in SO2, CO, PM2.5, NO2 and PM10; these concentrations were 43.4%, 34.6%, 21.4%, 17.4%, and 14.2% lower in P-II than P-I, respectively. But the concentration of O3 had no obvious improvement. The higher sandstorm frequency in P-II led to no significant decrease in the ERtotal and even resulted in an increase in the average ERtotal in cities located in northwestern Gansu from 0.78% in P-I to 1.0% in P-II. The cumulative distribution of NHAQI-based population-weighted exposure revealed that 24% of the total population was still exposed to light pollution in spring during P-II, while the air quality in other three seasons had significant improvements and all people were under healthy air quality level.

Greater variability in HDL-C was associated with an increased risk of cognitive decline in the middle- and elderly Chinese: A cohort study.

BACKGROUND: Previous studies into relationship between high-density lipoprotein cholesterol (HDL-C) and cognitive decline were constrained to a single measurement, leaving the association between HDL-C variability and risk of cognitive decline unclear. METHODS: We identified 5930 participants from the China Health and Retirement Longitudinal Study (CHARLS) who were devoid for stroke, dementia, and memory-related diseases at baseline and underwent a minimum of 2 sequential health examinations during 2011-2015. Variability in HDL-C was defined as (1) variability independent of the mean (VIM), (2) average real variability (ARV), and (3) standard deviation (SD) of HDL-C change from baseline and follow-up visits. Cognitive function was evaluated in 2018 by Mini-mental state examination (MMSE) in the Chinese version. Logistic regression was employed to explore the association between HDL-C variability and cognitive decline. Odd ratios (OR) and 95 % confidence intervals (CI) were reported. RESULTS: The study included participants from CHARLS, mean age of 57.84±8.44 years and 44 % male. After adjustment for covariates, the highest quartile of VIM was associated with an increased risk of cognitive decline [OR:1.049, 95 %CI: 1.014-1.086] compared to the lowest quartile. For each SD increment of VIM, the OR was 1.015 (95 %CI:1.003-1.027). Strong dose-response relationships were identified (P for trend: 0.005). Consistent results were obtained for other measures of HDL-C variability (ARV and SD). Similar patterns were identified in different dimensions of cognition. CONCLUSIONS: Elevated HDL-C variability was associated with increased cognitive decline risk. Strategies to reducing HDL-C variability may lower the risks of cognitive decline among the general population.

Highly integrated automatic injection terahertz microfluidic biosensor based on metasurface and LT-GaAs photoconductive antenna.

In this paper, a highly integrated terahertz (THz) biosensor is proposed and implemented, which pioneered the preparation of low-temperature gallium arsenide (LT-GaAs) thin film photoconductive antenna (PCA) on the sensor for direct generation and detection of THz waves, simplifying complex terahertz time-domain spectroscopy (THz-TDS) systems. A latch type metasurface is deposited in the detection region to produce a resonance absorption peak at 0.6 THz that is independent of polarisation. Microfluidics is utilised and automatic injection is incorporated to mitigate the experimental effects of hydrogen bond absorption of THz waves in aqueous-based environment. Additionally, cell damage is minimised by regulating the cell flow rate. The biosensor was utilised to detect the concentration of three distinct sizes of bacteria with successful results. The assay was executed as a proof of concept to detect two distinct types of breast cancer cells. Based on the experimental findings, it has been observed that the amplitude and blueshift of the resonance absorption peaks have the ability to identify and differentiate various cancer cell types. The findings of this study introduce a novel approach for developing microfluidic THz metasurface biosensors that possess exceptional levels of integration, sensitivity, and rapid label-free detection capabilities.

Effectiveness of mobile health applications on clinical outcomes and health behaviors in patients with coronary heart disease: A systematic review and meta-analysis.

Objective: Mobile health applications (apps) have gained significant popularity and widespread utilization among patients with coronary heart disease (CHD). The objective of this study is to evaluate the effects of mHealth apps on clinical outcomes and health behaviors in patients with CHD. Methods: Databases were searched from inception until December 2023, including Cochrane Library, PubMed, EMBASE, Web of Science, CINAHL, China National Knowledge Infrastructure (CNKI), Chinese BioMedical Literature Service System (SinoMed), Wanfang Data, China Science and Technology Journal Database (VIP), for randomized controlled trials (RCTs) regarding the effectiveness of mHealth apps in patients with CHD. Two researchers conducted a comprehensive review of the literature, extracting relevant data and evaluating each study's methodological quality separately. The meta-analysis was performed utilizing Review Manager v5.4 software. Results: A total of 34 RCTs were included, with 5,319 participants. The findings demonstrated that using mHealth apps could decrease the incidence of major adverse cardiac events (RR = 0.68, P = 0.03), readmission rate (RR = 0.56, P < 0.001), total cholesterol (WMD = -0.19, P = 0.03), total triglycerides (WMD = -0.24, P < 0.001), waist circumference (WMD = -1.92, P = 0.01), Self-Rating Anxiety Scale score (WMD = -6.70, P < 0.001), and Self-Rating Depression Scale score (WMD = -7.87, P < 0.001). They can also increase the LVEF (WMD = 6.50, P < 0.001), VO2 max (WMD = 1.89, P < 0.001), 6-min walk distance (6MWD) (WMD = 19.43, P = 0.004), Morisky Medication Adherence Scale-8 score (WMD = 0.96, P = 0.004), and medication adherence rate (RR = 1.24, P = 0.03). Nevertheless, there is no proof that mHealth apps can lower low-density lipoprote in cholesterol, blood pressure, BMI, or other indicator (P > 0.05). Conclusion: Mobile health apps have the potential to lower the incidence of major adverse cardiac events (MACEs), readmission rates, and blood lipids in patients with CHD. They can also help enhance cardiac function, promote medication adherence, and alleviate symptoms of anxiety and depression. To further corroborate these results, larger-scale, multi-center RCTs with longer follow-up periods are needed.

Pacidusin B isolated from Phyllanthus acidus triggers ferroptotic cell death in HT1080 cells.

Cancer cells generally exhibit 'iron addiction' phenotypes, which contribute to their vulnerability to ferroptosis inducers. Ferroptosis is a newly discovered form of programmed cell death caused by iron-dependent lipid peroxidation. In the present study, pacidusin B, a dichapetalin-type triterpenoid from Phyllanthus acidus (L.) Skeels (Euphorbiaceae), induces ferroptosis in the HT1080 human fibrosarcoma cell line. Cells treated with pacidusin B exhibited the morphological characteristic 'ballooning' phenotype of ferroptosis. The biochemical hallmarks of ferroptosis were also observed in pacidusin B-treated cells. Both oxidative stress and ER stress play significant roles in pacidusin B-induced ferroptosis. The activation of the PERK-Nrf2-HO-1 signaling pathway led to iron overload, while inhibition of GPX4 further sensitized cancer cells to ferroptosis. Furthermore, the molecular docking study showed that pacidusin B docked in the same pocket in xCT as the ferroptosis inducer erastin. These results revealed that pacidusin B exerts anticancer effects via inducing ER-mediated ferroptotic cell death.

Tumor-derived extracellular vesicles as a biomarker for breast cancer diagnosis and metastasis monitoring.

It is imperative to explore biomarkers that are both precise and readily accessible in the comprehensive management of breast cancer. A multicenter cohort, including 512 breast cancer patients and 198 nonneoplastic individuals, was recruited to detect the level of tumor-derived extracellular vesicles using our method based on dual DNA tetrahedral nanostructures. The level of tumor-derived extracellular vesicles was significantly higher in newly diagnosed breast cancer patients than in nonneoplastic individuals at a cutoff value of 3.58 U/µL. For postoperative metastasis monitoring, the level of tumor-derived extracellular vesicles was significantly higher in breast cancer patients with metastasis than in those without metastasis at a cutoff value of 3.91 U/µL. Its efficacy of diagnosis and metastasis monitoring was superior to traditional tumor markers. Elevated level of tumor-derived extracellular vesicles served as a predictive biomarker for diagnosis and metastasis monitoring in breast cancer patients.

Influence of topography and synoptic weather patterns on air quality in a valley basin city of Northwest China.

To clarify the mechanism underlying the effects of weather patterns and topography on air pollution, this study conducted the obliquely rotated principal component analysis in the T-mode to analyze ERA5 reanalysis data and categorize typical weather patterns at a 700-hPa geopotential height from 2015 to 2022. The probability of worsened air pollution attributable to weather patterns was quantitatively assessed using a generalized additive model. The results indicated that due to the influence of topography, Lanzhou was affected by an extended period of downdraft (with weak convective intensity) and the delayed formation of a convective boundary layer during the daytime by 1-2 h relative to other areas. Under the combined effect of low trough patterns (south low pressure type [SL] and south low weak pressure type [SL-]) and topography, the formation of a stable layer above the planetary boundary layer (PBL) would weaken the vertical exchange of the local airflow and inhibit the development of the PBL. The type of SL led to the most severe pollution, causing a 61.9 % (95 % confidence interval [CI]: 46.3 %-79.3 %) increase in PM2.5 concentration. For southwest high pressure patterns (south high [SH], southwest weak high [SWH-], southwest high [SWH], and southwest strong high [SWH+] pressure types), the prevailing northwest wind was the main transport path for pollutants. For the high pressure patterns (north high [NH] and northwest high [NWH] pressure types) and south wind patterns (southeast weak high [SEH-], southeast high [SEH], and northeast high [NEH] pressure types), the enhancement of vertical convection, deepening of the PBL, and reduction of pollution transport led to improved air quality. The NH, NWH, and NEH pressure types caused PM2.5 concentration to decrease by 18.4 % (95 % CI: 8.8 %-27.1 %), 14.9 % (95 % CI: 4.7 %-24.0 %), and 35.9 % (95 % CI: 9.7 %-54.6 %), respectively.

Is cognitive behavioral therapy for insomnia more cost-effective? New-perspective on economic evaluations: a systematic review and meta-analysis.

STUDY OBJECTIVES: To investigate the cost-effectiveness of cognitive behavioral therapy for insomnia (CBTI), with an additional focus on digital CBTI (dCBTI) in adults with insomnia. METHODS: We searched eight electronic databases for economic evaluations of CBTI: PubMed, Scopus, Web of Science, psycINFO, Cochrane, Library, CINAHL, ProQuest, and National Health Service Economic Evaluation Database. Meta-analyses were performed to investigate the effects and costs between CBTI and control groups (no treatment, other treatments included hygiene education and treatment as usual). Subgroup analyses for dCBTI were conducted. RESULTS: Twelve randomized controlled trial studies between 2004 and 2023 were included in our systematic review and meta-analyses. The incremental cost-utility ratios and incremental cost-effectiveness ratios showed that the CBTI and dCBTI groups were more cost-effective than controls, from healthcare perspective and societal perspective, respectively. Compared to controls, CBTI demonstrated significantly better efficacy within 12 months. Healthcare costs were significantly higher in the CBTI groups compared to the controls within 6 months but there was no difference at 12 months. Additionally, dCBTI was associated with significantly lower presenteeism costs compared to controls at 6 months. CONCLUSIONS: Our findings suggest that CBTI is more cost-effective than other treatments or no treatment for adults with insomnia. It may bring more economic benefits in the long term, especially in long-lasting efficacy and cost reduction. In addition, dCBTI is one of the cost-effective options for insomnia. PROSPERO REGISTRATION NUMBER: CRD42 022 383 440. URL: www.crd.york.ac.uk/PROSPERO. NAME FOR PROSPERO REGISTRATION: Cost-effectiveness of cognitive behavioral therapy for insomnia (CBTI): a systematic review with meta-analysis.

Rasch analysis of the pre-sleep arousal scale in patients with acute insomnia disorder.

BACKGROUND: Hyperarousal plays an essential role in the initiation and maintenance of insomnia, highlighting the need for a tool that measure the hyperarousal state during the early course of insomnia. Pre-sleep Arousal Scale (PSAS) is a self-report questionnaire to evaluate subjective pre-sleep arousal of insomnia. The aim of this study was to examine the psychometric properties of the PSAS among patients with acute insomnia disorder (AID) using Rasch analysis. METHODS: Totally 170 patients with AID from 31 public hospitals in China were recruited and completed the test. The psychometric properties of the PSAS were tested using Rasch analysis by Winsteps v5.4.1.0, including unidimensionality, local item independence, item fit, category diagnostics, reliability, item-person maps and differential item functioning (DIF) by age and gender. RESULTS: According to Rasch analysis, somatic and cognitive subscales were unidimensional and basically demonstrated good item-fit statistics. 4-point Likert scale may be more appropriate for PSAS. All items have a good reliability and separation. No gender and age bias were detected for the scale. However, the person arousal level is not well matched to item difficulty. CONCLUSION: The present study further reveals appropriate psychometric properties of the PSAS in patients with AID and provides suggestions for refinements and supplements to the PSAS.

Endoscopic Submucosal Dissection Criteria for Differentiated-type Early Gastric Cancer Are Applicable to Mixed-type Differentiated Predominant.

BACKGROUND: There is a lack of sufficient evidence on whether mixed-type differentiated predominant early gastric cancer (MD-EGC) can be treated endoscopically by referring to the criteria for differentiated-type early gastric cancer (EGC). This study aims to evaluate the efficacy of endoscopic submucosal dissection (ESD) in MD-EGC. METHODS: Patients with differentiated-type EGC treated with ESD first from January 2015 to June 2021 were reviewed, including MD-EGC and pure differentiated-type EGC (PD-EGC). Clinical data, including the clinicopathological characteristics, resection outcomes of ESD, and recurrence and survival time, were collected, and the difference between MD-EGC and PD-EGC was tested. RESULTS: A total of 48 patients (48 lesions) with MD-EGC and 850 patients (890 lesions) with PD-EGC were included. Compared with PD-EGC, MD-EGC had a higher submucosal invasion rate (37.5% vs. 13.7%, P<0.001) and lymphatic invasion rate (10.4% vs. 0.4%, P<0.001). The rates of complete resection (70.8% vs. 92.5%, P<0.001) and curative resection (54.2% vs. 87.4%, P<0.001) in MD-EGC were lower than those of PD-EGC. Multivariate analysis revealed that MD-EGC (OR 4.26, 95% CI, 2.22-8.17, P<0.001) was an independent risk factor for noncurative resection. However, when curative resection was achieved, there was no significant difference in the rates of recurrence (P=0.424) between the 2 groups, whether local or metachronous recurrence. Similarly, the rates of survival(P=0.168) were no significant difference. CONCLUSIONS: Despite the greater malignancy and lower endoscopic curative resection rate of MD-EGC, patients who met curative resection had a favorable long-term prognosis.

Ubiquitin ligase TRIM15 promotes the progression of pancreatic cancer via the upregulation of the IGF2BP2-TLR4 axis.

BACKGROUND: The tripartite motif family, predominantly characterized by its E3 ubiquitin ligase activities, is involved in various cellular processes including signal transduction, apoptosis and autophagy, protein quality control, immune regulation, and carcinogenesis. Tripartite Motif Containing 15 (TRIM15) plays an important role in melanoma progression through extracellular signal-regulated kinase activation; however, data on its role in pancreatic tumors remain lacking. We previously demonstrated that TRIM15 targeted lipid synthesis and metabolism in pancreatic cancer; however, other specific regulatory mechanisms remain elusive. METHODS: We used transcriptomics and proteomics, conducted a series of phenotypic experiments, and used a mouse orthotopic transplantation model to study the specific mechanism of TRIM15 in pancreatic cancer in vitro and in vivo. RESULTS: TRIM15 overexpression promoted the progression of pancreatic cancer by upregulating the toll-like receptor 4. The TRIM15 binding protein, IGF2BP2, could combine with TLR4 to inhibit its mRNA degradation. Furthermore, the ubiquitin level of IGF2BP2 was positively correlated with TRIM15. CONCLUSIONS: TRIM15 could ubiquitinate IGF2BP2 to enhance the function of phase separation and the maintenance of mRNA stability of TLR4. TRIM15 is a potential therapeutic target against pancreatic cancer.

Ursolic acid alleviates meiotic abnormalities induced by 3-nitropropionic acid in mouse oocytes.

3-nitropropionic acid (3-NPA), a toxic metabolite produced by mold, is mainly found in moldy sugarcane. 3-NPA inhibits the activity of succinate dehydrogenase that can induce oxidative stress injury in cells, reduce ATP production and induce oxidative stress in mouse ovaries to cause reproductive disorders. Ursolic acid (UA) has a variety of biological activities and is a pentacyclic triterpene compound found in many plants. This experiment aimed to investigate the cytotoxicity of 3-NPA during mouse oocyte in vitro maturation and the protective effects of UA on oocytes challenged with 3-NPA. The results showed that UA could alleviate 3-NPA-induced oocyte meiotic maturation failure. Specifically, 3-NPA induced a decrease in the first polar body extrusion rate of oocytes, abnormal distribution of cortical granules, and an increase in the proportion of spindle abnormalities. In addition, 3-NPA caused mitochondrial dysfunction and induced oxidative stress, including decreases in the GSH, mitochondrial membrane potential and ATP levels, and increases in the ROS levels, and these effects led to apoptosis and autophagy. The addition of UA could significantly improve the adverse effects caused by 3-NPA. In general, our data show that 3-NPA affects the normal development of oocytes during the in vitro culture, and the addition of UA can effectively repair the damage caused by 3-NPA to oocytes.

Dihydroartemisinin Protects Mice from CUMS-induced Depression-like Behaviors by Regulating Gut Microbes.

Depression is one of the most common forms of psychopathology, which is associated with gut microbiota dysfunction. Dihydroartemisinin (DHA) has been shown to regulate gut microbiota and ameliorate neuropathies, but whether it can be used to treat depression remains unclear. Our study found that DHA treatment raised the preference for sugar water in chronic unpredictable mild stress (CUMS)-induced mice and reduced the immobility time in open field, forced swimming and tail suspension experiments, and promoted doublecortin expression. Additionally, DHA up-regulated the diversity and richness of intestinal microbiota in depression-like mice, and restored the abnormal abundance of microbiota induced by CUMS, such as Turicibacter, Lachnospiraceae, Erysipelotrichaceae, Erysipelatoclostridium, Eubacterium, Psychrobacter, Atopostipes, Ileibacterium, Coriobacteriacea, Alistipes, Roseburia, Rikenella, Eggerthellaceae, Ruminococcus, Tyzzerella, and Clostridia. Furthermore, KEGG pathway analysis revealed that gut microbiota involved in the process of depression may be related to glucose metabolism, energy absorption and transport, and AMPK signaling pathway. These results indicated that DHA may play a protective role in CUMS-induced depression by mediating gut-microbiome.