Restoring glucose balance: Conditional HMGB1 knockdown mitigates hyperglycemia in a Streptozotocin induced mouse model.

Diabetes mellitus (DM) poses a significant global health burden, with hyperglycemia being a primary contributor to complications and high morbidity associated with this disorder. Existing glucose management strategies have shown suboptimal effectiveness, necessitating alternative approaches. In this study, we explored the role of high mobility group box 1 (HMGB1) in hyperglycemia, a protein implicated in initiating inflammation and strongly correlated with DM onset and progression. We hypothesized that HMGB1 knockdown will mitigate hyperglycemia severity and enhance glucose tolerance. To test this hypothesis, we utilized a novel inducible HMGB1 knockout (iHMGB1 KO) mouse model exhibiting systemic HMGB1 knockdown. Hyperglycemic phenotype was induced using low dose streptozotocin (STZ) injections, followed by longitudinal glucose measurements and oral glucose tolerance tests to evaluate the effect of HMGB1 knockdown on glucose metabolism. Our findings showed a substantial reduction in glucose levels and enhanced glucose tolerance in HMGB1 knockdown mice. Additionally, we performed RNA sequencing analyses, which identified potential alternations in genes and molecular pathways within the liver and skeletal muscle tissue that may account for the in vivo phenotypic changes observed in hyperglycemic mice following HMGB1 knockdown. In conclusion, our present study delivers the first direct evidence of a causal relationship between systemic HMGB1 knockdown and hyperglycemia in vivo, an association that had remained unexamined prior to this research. This discovery positions HMGB1 knockdown as a potentially efficacious therapeutic target for addressing hyperglycemia and, by extension, the DM epidemic. Furthermore, we have revealed potential underlying mechanisms, establishing the essential groundwork for subsequent in-depth mechanistic investigations focused on further elucidating and harnessing the promising therapeutic potential of HMGB1 in DM management.

Willingness to accept metaverse safety training for construction workers based on extended UTAUT.

Safety training (ST) is essential in avoiding unsafe behavior of construction workers. With the rise of metaverse technology, metaverse safety training (MST) has gradually become a new model to guide construction workers in safety production. An in-depth study of construction workers' willingness to accept the metaverse safety training (WAMST) helps improve its effectiveness, but studies need to pay more attention to it. This study constructs a conceptual model of WAMST for construction workers, and the influencing factors of WAMST are explained based on the extended Unified Theory of Acceptance and Use of Technology (UTAUT). It established a Structural equation modeling to verify the relationship between influencing factors. An example verifies the feasibility of the model. The results show that the framework significantly contributes to the willingness of construction workers to participate and improves safety awareness. Specifically, performance expectancy, effort expectancy, social influence, and convenient conditions significantly affect the construction workers' willingness to accept. Convenient conditions have a direct effect on actual behavior. Willingness to accept plays a mediating role between performance expectancy and actual behavior. Perceived trust moderates the effect between willingness to accept and actual behavior, and the force of positive interpretation increases proportionally. It confirms how to improve the safety capacity of construction workers and provides references for governments, enterprises, and projects to formulate ST strategies.

A New Method to Assist Decision-Making of Water Environmental Emergency in Expressway Region.

Water environmental emergency (WEE) in expressway region is a special kind of risk event with several characteristics, such as rarity, unconventionality, and harmfulness. The emergency decision-making (EDM) features, procedures, and methods are considerably different from the general decision-making problems. EDM quality is directly related to the timely implementation of a reasonable emergency plan. Therefore, methods should be developed to respond to emergencies immediately and scientifically and minimize the damage to water environment. This work introduces risk source identification and emergency classification and develops an emergency decision model based on scenario retrieval and case-based reasoning, according to the existing EDM model and characteristics of WEE in expressway region. The proposed method is validated through case analysis of Daguang expressway in China. This method provides an effective solution for EDM of WEEs in expressway region. The emergency measures can be implemented quickly and effectively after the occurrence of water environmental emergencies to control pollution events, provide scientific and feasible action guides for emergency processes, and enrich the case base of decision-making systems.

How to Promote Urban Intelligent Transportation: A Fuzzy Cognitive Map Study.

As an important part of smart city, intelligent transportation is an critical breakthrough to solve urban traffic congestion, build an integrated transportation system, realize the intelligence of traffic infrastructure and promote sustainable development of traffic. In order to investigate the construction of intelligent transportation in cities, 20 initial affecting variables were determined in this study based on literature analysis. A questionnaire collected from professionals in intelligent transportation was conducted, and a total of 188 valid responses were received. Then the potential grouping was revealed through exploratory factor analysis. Finally, a causal model containing seven concepts was established using the practical experience and knowledge of the experts. A root cause analysis method based on fuzzy cognitive map (FCM) was also proposed to simulate intelligent transportation construction (ITC). The results indicate:(1) The 20 variables can be divided into six dimensions: policy support (PS), traffic sector control (TSC), technical support (TS), communication foundation (CF), residents' recognition (RR), and talent quality (TQ); and (2) In the FCM model, all six concept nodes (PS, TSC, TS, CF, RR, and TQ) have a significant positive correlation with the target concept node ITC. The rank of the six dimensions according to correlation strength is TS, CF, PS, TSC, RR, and TQ. The findings of this paper can help academics and practitioners understand the deep-seated determinants of urban intelligent transportation construction more comprehensively, and provide valuable suggestions for policy makers. And thus, the efficiency of intelligent transportation construction can be improved.

Electrical Dry Needling Plus Corticosteroid Injection for Osteoarthritis of the Knee: A Randomized Controlled Trial.

OBJECTIVE: To investigate the effects of electrical dry needling (DN) plus corticosteroid injection (CSI) on pain, physical function, and global change in patients with osteoarthritis of the knee (KOA). DESIGN: A prospective, single-blinded, randomized controlled trial. SETTING: Pain treatment clinic. PARTICIPANTS: Sixty patients with KOA were randomly assigned to the electrical dry needling plus corticosteroid injection (electrical-DN+CSI) group or CSI group. INTERVENTIONS: The CSI group received glucocorticoid injection only once during the trial, and the electrical-DN+CSI group received glucocorticoid injection combined with 4 sessions of electrical-DN. MAIN OUTCOMES MEASURES: The primary outcome was the numerical rating scale at 3 months. The secondary outcomes were the Western Ontario and McMaster Universities Osteoarthritis Index, the time to complete the Timed Up and Go test, and the score of the global rating of change scale at 3 months. A generalized linear mixed-effects model was used to analyze the repeated measurement data. RESULTS: Baseline characteristics and measurements were similar in the 2 groups. The group by time interaction effect was significant for all variables (P<.05). The electrical-DN+CSI group obtained a more significant reduction in pain intensity and more significant improvement in dysfunction than the CSI group at 3 months (P<.05). The median global rating of change score for the CSI group was +3 (somewhat better), and that for the electrical-DN+CSI group was +4 (moderately better). CONCLUSION: Electrical-DN therapy at myofascial trigger points combined with CSI is more effective at alleviating pain, improving dysfunction, and creating global change than CSI alone for patients with KOA. Electrical-DN may be an essential part of treatment for KOA rehabilitation.

Mitomycin C Inhibits Esophageal Fibrosis by Regulating Cell Apoptosis and Autophagy via lncRNA-ATB and miR-200b.

Benign esophageal strictures (BESs) frequently results from esophageal fibrosis. The transformation of fibroblasts into fibrocyte is an important cause of fibrosis. The treatment of fibrosis is challenging. Some previous studies have indicated the antifibrotic effect of mitomycin C (MMC). However, the mechanism of action of MMC and its optimal dose for treatment remains unclear. In the present study, the role of MMC in fighting fibrosis and its mechanism was investigated. Human esophageal fibroblast cells (HEFs)were treated without or with MMC, at 2, 5, 10 µg/ml, combining with mimic lncRNA-ATB, miR-200b inhibitor, rapamycin (RAPA), and 3-Methyladenine (3-MA). The cell viability, and cell apoptosis were evaluated. In addition, expression of apoptosis related proteins (caspase8 and caspase3), autophagy related proteins (LC3II and ATG5) and fibrosis related proteins (α-SMA collagen-1 and TGF-ß) were also evaluated. Furthermore, autophagosome was observed by transmission electron microscope. Results showed that the expression of lncRNA-ATB was down-regulated and miR-200b was up-regulated after treated with MMC. And MMC induced cell apoptosis and inhibited cell autophagy. On the other hand, RAPA, mimic lncRNA-ATB and miR-200b inhibitor reduced fibrogenic effect of MMC on HEFs. Collectively, this study suggests that MMC inhibited esophageal fibrosis by regulating cell apoptosis and autophagy via downregulating lncRNA-ATB and upregulating miR-200b.

The Long Noncoding RNA MAGI1-IT1 Regulates the miR-302d-3p/IGF1 Axis to Control Gastric Cancer Cell Proliferation.

BACKGROUND: MAGI1-IT1 is a long non-coding RNA (lncRNA) previously reported to regulate several cancer types, but its functional role in gastric cancer (GC) remains to be defined. This study therefore explored the mechanistic role played by MAGI1-IT1 in the regulation of GC cell proliferation. METHODS: 120 pairs of GC patient tumor, paracancerous tissues, human GES-1 control cells and human AGS, MKN-74, MKN-45, and MGC-803 GC cell lines were used to detected MAGI1-IT1, miR-302d-3p, and IGF1 expression by a qPCR approach. An shRNA approach was used to knock down MGI1-IT1 in order to examine the effect of such treatment on GC cell proliferation, and rescue experiments were subsequently conducted. In addition, the functional role of MAGI1-IT1 in GC in vivo was evaluated with a xenograft model system. P < 0.05 was the significance threshold. RESULTS: Elevated MAGI1-IT1 expression was detected in GC cell lines and tissues, and was linked to poorer patient overall survival. Knocking down this lncRNA disrupted GC cell proliferation in vitro and in vivo, and miR-302d-3p was identified as a MAGI1-IT1 target. Notably, miR-302d-3p inhibition partially reversed the impact of MAGI1-IT1 knockdown on GC cell proliferation. IGF1 was subsequently identified as a miR-302d-3p target gene that was upregulated by MAGI1-IT1 through miR-302d-3p. CONCLUSION: Overall, these results indicated that MAGI1-IT1 controlled GC cell proliferation by modulating the miR-302d-3p/IGF1 axis, suggesting that this may be a viable treatment target in those with GC.

Intrinsically ESIPT-exhibiting and enhanced emission in polymer nanoparticles as signaling for sensing nitrite.

A straightforward approach to the fabrication of intrinsically excited-state intramolecular proton transfer (ESIPT)-fluorescent polymer nanoparticles (e-PNPs) was developed. The e-PNPs were obtained by self-assembly of the homopolymers derived from 4-aminosalicylic acid in aqueous solution. By incorporating ESIPT modules into polymer nanoparticles, the ESIPT reaction can be endowed with moderate hydrophobic micro-environment by nanoparticle scaffolds, eliciting enhanced ESIPT emission. The newly developed e-PNPs exhibit strong tautomeric fluorescence(e-FL), good photostability, low-toxicity and favourable biocompatibility in aqueous solution. Upon the addition of NO2-, the e-FL can be significantly quenched owing to the reaction of NO2- with the amide groups on e-PNPs. From this basis, the fluorescence detection of NO2- was implemented, which showed a linear relationship between 0 nM and 110 nM with a detection limit of 2.3 nM. Furthermore, e-PNPs were used as nanoprobes to monitor the NO2- levels in HeLa cells by fluorescence imaging, demonstrating the ability of discrimination from different concentrations of NO2-. The proposed method can be applied to a wide range of other ESIPT modules to integrate into polymer nanoparticles and offer highly sensitive nanosensing platform for bioanalysis and molecular imaging.

[Estradiol regulates the expression of small conductance Ca(2)+ activated K(+) channel 3 in rat colonic smooth muscle cells in an estrogen receptor α-dependent manner].

OBJECTIVE: To explore the effects and possible mechanism of 17ß-estradiol on the expression of small conductance Ca(2+) activated K(+) channel 3 (SK3) in rat colonic smooth muscle cells (SMC). METHODS: The SMC isolated from male SD rats by enzymolysis were cultured. And double immunofluorescence staining was used to detect the co-expression of SK3 and α-actin. Colonic SMC were cultured with different concentrations of 17ß-estradiol for 24 h or with 50 nmol/L 17ß-estradiol at different time points respectively. The expressions of SK3 in colonic SMC were measured by real-time quantitative reverse transcription (qRT)-PCR and Western blotting. The effects of estrogen receptor (ER) inhibitor ICI 182780, albumin bovine serum-17ß-estradiol (BSA-E2), ERα selective agonist propyl pyrazole triol (PPT) and ERß selective agonist diarylpropionitrile (DPN) on SK3 expression were observed. RESULTS: Double immunofluorescence staining showed that SK3 and α-actin co-expressed in cultured colonic SMC. The expression of SK3 of 17ß-estradiol at different concentration (10, 50 nmol/L) significantly higher than the control group (protein: 0.217 ± 0.030 and 0.321 ± 0.077 vs 0.103 ± 0.063, mRNA: 1.872 ± 0.606 and 2.967 ± 0.659 vs 0.813 ± 0.202, all P < 0.05). And 50 nmol/L was the most effective in vitro concentration. The peak expression of SK3 appeared at 12 and 24 hour (2.91 and 3.30-fold in protein vs 3.46 and 3.37-fold in mRNA respectively, all P < 0.05). The protein levels of SK3 in ICI 182780 plus 17ß-estradiol group was less than 17ß-estradiol group (0.111 ± 0.050 vs 0.351 ± 0.084, P < 0.05). But it was not influenced by BSA-E2. The expressions of SK3 in PPT and E2 groups were both higher than control group (0.270 ± 0.071, 0.309 ± 0.052 vs 0.087 ± 0.018, both P < 0.05) . However DPN had no effect on SK3 protein levels. CONCLUSIONS: SK3 is localized in rat colonic SMC. And 17ß-estradiol increases its expression in an ERα-dependent manner.