The transcription factor MdBPC2 alters apple growth and promotes dwarfing by regulating auxin biosynthesis.

Auxin plays important roles throughout plant growth and development. However, the mechanisms of auxin regulation of plant structure are poorly understood. In this study, we identified a transcription factor (TF) of the BARLEY B RECOMBINANT/BASIC PENTACYSTEINE (BBR/BPC) family in apple (Malus × domestica), MdBPC2. It was highly expressed in dwarfing rootstocks, and it negatively regulated auxin biosynthesis. Overexpression of MdBPC2 in apple decreased plant height, altered leaf morphology, and inhibited root system development. These phenotypes were due to reduced auxin levels and were restored reversed after exogenous indole acetic acid (IAA) treatment. Silencing of MdBPC2 alone had no obvious phenotypic effect, while silencing both Class I and Class II BPCs in apple significantly increased auxin content in plants. Biochemical analysis demonstrated that MdBPC2 directly bound to the GAGA-rich element in the promoters of the auxin synthesis genes MdYUC2a and MdYUC6b, inhibiting their transcription and reducing auxin accumulation in MdBPC2 overexpression lines. Further studies established that MdBPC2 interacted with the polycomb group (PcG) protein LIKE HETEROCHROMATIN PROTEIN 1 (LHP1) to inhibit MdYUC2a and MdYUC6b expression via methylation of histone 3 lysine 27 (H3K27me3). Silencing MdLHP1 reversed the negative effect of MdBPC2 on auxin accumulation. Our results reveal a dwarfing mechanism in perennial woody plants involving control of auxin biosynthesis by a BPC transcription factor, suggesting its use for genetic improvement of apple rootstock.

Knowledge, attitudes, and practices of endoscopy among gastroenterologists in diagnosis and management of inflammatory bowel disease in China: a multicenter cross-sectional study.

BACKGROUND: The aim was to assess the knowledge, attitudes, and practices (KAPs) of endoscopy among gastroenterologists in the diagnosis and management of IBD in China. METHODS: A multicenter cross-sectional KAP study was performed. The questionnaire was developed and improved using feedback and opinions from a team of experienced IBD specialist professors and then distributed and collected online. In addition, eight fellow gastroenterologists participated in an IBD endoscopy training program were asked to review endoscopic images, and the consistency of the endoscopic scores before and after training was calculated. RESULTS: A total of 193 participants from 12 provincial-level administrative regions encompassing both the Northern and Southern parts of China completed the study questionnaire. The median age of the participants was 40 (36, 45) years, with the majority being female (70.5%). The median professional experience as gastroenterologists was 11 (7, 17) years, while the median experience as endoscopists was 8 (3, 15) years. The median knowledge score was 8 out of 10 points for single-choice questions; however, most gastroenterologists believed that some concepts in these endoscopic indices were vague, including those regarding deep ulcerations, ulcerated surfaces, affected surfaces and narrowing in open-answer questions. The UCEIS and SES-CD were considered most consistent with clinical activity score in the evaluation of UC and CD, respectively. IBD subspecialists and gastroenterologists who had previously received IBD endoscopy screening training were more likely to use endoscopic indices (p<0.001, p = 0.029, respectively). The Rutgeerts score demonstrated the most significant improvement in consistency before and after training, from 0.407 (95% CI: 0.025-0.999) to 0.909 (95% CI: 0.530-1.000). CONCLUSIONS: We propose the elucidation of ambiguous definitions in endoscopic indices, enhancement of training, and the application of innovative technology to enhance the application of endoscopic evaluation and endoscopic indices in clinical practice.

Meta-analysis on Asymptomatic Endometrial Thickening and Its Association with Endometrial Cancer Risk in Women Over 50 Years of Age.

Purpose: This study systematically assesses the correlation between asymptomatic endometrial thickening after the age of 50 and the risk of endometrial cancer (EC). Methods: A comprehensive search was conducted using the Cochrane Library, Web of Science, PubMed, ProQuest, and Chinese biomedical literature databases Wanfang, Weipu, and CNG until August 2022. The included literature was analyzed using RevMan 5.3 software to explore heterogeneity in each study. Results: Five studies were finally included. The assessment of odds ratio (OR) heterogeneity between women with endometrial thickening and the risk of EC showed P = .18, I2=95%, indicating significant heterogeneity. A random-effects model was applied for meta-analysis, revealing a result of 0.96, 95% CI (0.92, 1.02), P = .18, indicating no statistical significance between the two groups (P > .05). The funnel plot demonstrated asymmetry, suggesting evident publication bias. Conclusion: There is no consistent correlation between asymptomatic endometrial thickening and the occurrence of EC in individuals over 50 years of age.

Reactivation of tumour suppressor in breast cancer by enhancer switching through NamiRNA network.

Dysfunction of Tumour Suppressor Genes (TSGs) is a common feature in carcinogenesis. Epigenetic abnormalities including DNA hypermethylation or aberrant histone modifications in promoter regions have been described for interpreting TSG inactivation. However, in many instances, how TSGs are silenced in tumours are largely unknown. Given that miRNA with low expression in tumours is another recognized signature, we hypothesize that low expression of miRNA may reduce the activity of TSG related enhancers and further lead to inactivation of TSG during cancer development. Here, we reported that low expression of miRNA in cancer as a recognized signature leads to loss of function of TSGs in breast cancer. In 157 paired breast cancer and adjacent normal samples, tumour suppressor gene GPER1 and miR-339 are both downregulated in Luminal A/B and Triple Negative Breast Cancer subtypes. Mechanistic investigations revealed that miR-339 upregulates GPER1 expression in breast cancer cells by switching on the GPER1 enhancer, which can be blocked by enhancer deletion through the CRISPR/Cas9 system. Collectively, our findings reveal novel mechanistic insights into TSG dysfunction in cancer development, and provide evidence that reactivation of TSG by enhancer switching may be a promising alternative strategy for clinical breast cancer treatment.

RNA binding protein POP7 regulates ILF3 mRNA stability and expression to promote breast cancer progression.

RNA binding proteins (RBPs) play pivotal roles in breast cancer (BC) development. As an RBP, Processing of precursor 7 (POP7) is one of the subunits of RNase P and RNase MRP, however, its exact function and mechanism in BC remain unknown. Here, we showed that expression of POP7 was frequently increased in BC cells and in primary breast tumors. Upregulated POP7 significantly promoted BC cell proliferation in vitro and primary tumor growth in vivo. POP7 also increased cell migration, invasion in vitro, and lung metastasis in vivo. Through RNA immunoprecipitation coupled with sequencing (RIP-seq), we found that POP7 bound preferentially to intron regions and POP7-binding peak associated genes were mainly enriched in cancer-related pathways. Furthermore, POP7 regulated Interleukin Enhancer Binding Factor 3 (ILF3) expression through influencing its mRNA stability. Knockdown of ILF3 significantly impaired the increased malignant potential of POP7-overexpressing cells, suggesting that POP7 enhances BC progression through regulating ILF3 expression. Collectively, our findings provide the first evidence for the important role of POP7 and its regulation of ILF3 in promoting BC progression.

circ-PSD3 promoted proliferation and invasion of papillary thyroid cancer cells via regulating the miR-7-5p/METTL7B axis.

Papillary thyroid cancer (PTC) is a common tumor malignancy of the endocrine system worldwide. Recently, circular RNAs (circRNAs) have been reported to participate in diverse pathological processes, especially in tumorigenesis. However, the functional role and mechanism of circRNA pleckstrin and Sec7 domain containing 3 (circ-PSD3) in PTC are still unclear. In this study, qRT-PCR results showed that circ-PSD3 was significantly upregulated in PTC tissues and cell lines. Meanwhile, circ-PSD3 overexpression was positively associated with larger tumor size, TNM stage, and lymph node metastasis. Knockdown of circ-PSD3 suppressed the proliferation and invasion of PTC cells. Besides, circ-PSD3 interacted with miR-7-5p to reduce its expression, and methyltransferase like 7B (METTL7B) was verified as a target gene of miR-7-5p. Functionally, inhibition of circ-PSD3 impeded PTC cell proliferation and invasion via targeting miR-7-5p to downregulate METTL7B expression. Taken together, silencing of circ-PSD3 hampered the proliferation and invasion of PTC cells via upregulating the inhibitory effect of miR-7-5p on METTL7B expression. Therefore, circ-PSD3 could be a potential diagnostic biomarker or molecular treatment target for PTC.

SQLE inhibition suppresses the development of pancreatic ductal adenocarcinoma and enhances its sensitivity to chemotherapeutic agents in vitro.

PURPOSE: In this study, we sought to explore the function of seven important enzymes (MSMO1, EBP, HMGCS1, IDI2, DHCR7, FDFT1, and SQLE) involved in cholesterol biosynthesis especially SQLE in PDAC therapy. METHODS AND RESULTS: The TCGA and Oncomine dataset were used to explore the expression of the seven enzymes in normal and cancerous pancreatic individual, and their anti-proliferation efficiency against PDAC cells was measured by cell viability assay. Expression level and prognostic values of SQLE were evaluated by western blot and Kaplan-Meier analysis. The influence of SQLE knockdown by shRNA in PDAC cells was assessed by transwell, colony formation and cell cycle analysis. RNA-seq and GSEA were utilized to investigate the potential mechanisms. The synergistic effect of SQLE inhibitor, terbinafine, combined with six chemotherapeutic drugs in PDAC cells was tested by CCK-8 method. We demonstrated that downregulation of those enzymes especially SQLE significantly suppressed PDAC cells survival. SQLE was upregulated in PDAC cell lines, and the elevated level of SQLE was correlated with poor prognosis in pancreatic cancer samples. SQLE knockdown could significantly inhibit the proliferation and migration of PDAC cells. Cell cycle was blocked in S phase after SQLE silencing. Mechanistically, GSEA analysis with RNA-seq data revealed that SQLE silencing negatively mediated mTORC1 and TNFα/NF-κB signaling pathways. Besides, SQLE inhibitor terbinafine enhanced chemotherapeutic sensitivity of the six compounds. CONCLUSIONS: This study demonstrated that SQLE was a novel target for PDAC therapy. The synergism role of SQLE inhibition and chemotherapy may be potential therapeutic strategy for pancreatic cancer treatment.

Fluorometric dopamine assay based on an energy transfer system composed of aptamer-functionalized MoS2 quantum dots and MoS2 nanosheets.

The authors describe a fluorometric strategy for the determination of dopamine (DA). It is based on the use of aptamer-functionalized MoS2 quantum dots (QDs) and MoS2 nanosheets (NSs). The QDs and NSs were extensively characterized with regard to their physical and chemical properties using methods such as TEM, XRD, FT-IR, EDX and molecular spectroscopies. The aptamer against dopamine was labeled with QDs acting as the energy donor in an energy transfer system, while the NSs serve as the energy acceptor. Under the optimal conditions, the fluorescence (FL) intensity (best measured at excitation/emission peaks of 315/412 nm) increases with increasing DA concentration in the range from 0.1 nM to 1000 nM, with a lower detection limit of 45 pM. The method was successfully applied to the determination of DA in complex matrices. In our perception, the method has a wide scope in that it may be extended to other biomolecules for which respective aptamer are available. The QDs show excellent optical properties, good stability, low cytotoxicity, and may also be applied to fluorometric imaging of live cells. Graphical abstract A "turn-on" fluorometric aptasensor for the determination of dopamine (DA) was established based on aptamer-functionalized molybdenum disulfide quantum dots (MoS2 QDs) and MoS2 nanosheets. This assay exhibits high selectivity and sensitivity with a detection limit as low as 45 pM.

MicroRNA-493 is a prognostic factor in triple-negative breast cancer.

Breast cancer is one of the most common malignant diseases in women. Triple-negative breast cancer (TNBC) shows higher aggressiveness and recurrence rates than other subtypes, and there are no effective targets or tailored treatments for TNBC patients. Thus, finding effective prognostic markers for TNBC could help clinicians in their ability to care for their patients. We used tissue microarrays (TMAs) to detect microRNA-493 (miR-493) expression in breast cancer samples. A miRCURY LNA detection probe specific for miR-493 was used in in situ hybridization assays. Staining results were reviewed by two independent pathologists and classified as high or low expression of miR-493. Kaplan-Meier survival plots and multivariate Cox analysis were carried out to clarify the relationship between miR-493 and survival. In the Kaplan-Meier analysis, patients with high miR-493 expression had better disease-free survival than patients with low miR-493 expression. After adjusting for common clinicopathological factors in breast cancer, the expression level of miR-493 was still a significant prognostic factor in breast cancer. Further subtype analysis revealed that miR-493 expression levels were only significantly prognostic in TNBC patients. These results were validated in the Molecular Taxonomy of Breast Cancer International Consortium database for overall survival. We proved the prognostic role of miR-493 in TNBC by using one of the largest breast cancer TMAs available and validated it in a large public RNA sequencing database.

Serum food specific IgG antibodies are associated with small bowel inflammation in patients with Crohn's disease.

BACKGROUND/AIMS: Food antigens are thought to play a vital role in the initiation and perpetuation of Crohn's disease (CD). The main purpose of this study was to evaluate the potential association of serum food specific IgG antibodies and small bowel (SB) inflammation in CD patients. METHODS: We conducted a prospective observational study with 96 CD patients. Demographic, disease-related data and inflammatory parameters were collected. Serum food IgG antibodies were measured using enzyme-linked immunosorbent assay (ELISA). Capsule endoscopy was performed to detect SB inflammation quantified by the Lewis Score. RESULTS: Seventy-eight of (81.3%) CD patients were detected positive for at least one food-specific antibody. The five most prevalent food antibodies in CD patients were tomato, egg, corn, rice, and soybean. Patients with SB inflammation had a higher positive rate of food IgG antibodies (P = 0.010) and more IgG-positive food items (P = 0.010) than those without. Specifically, patients with SB inflammation were more likely to have positive food-specific IgG against egg (P = 0.014), corn (P = 0.014), and wheat (P = 0.048). Additionally, the number of positive food IgGs ≥ 3 and elevated ESR were independently associated with concurrent SB inflammation (P = 0.015 and P = 0.013, respectively). CONCLUSION: Our study confirmed that CD patients with SB inflammation had a higher positive rate of food IgG antibodies and more IgG-positive food items. The number of food positive IgGs ≥ 3 and elevated ESR were independently associated with concurrent SB inflammation.

Comparison of organelle genomes between endangered mangrove plant Dolichandrone spathacea to terrestrial relative provides insights into its origin and adaptative evolution.

Dolichandrone spathacea is a mangrove associate with high medicinal and ecological values. However, due to the dual-pressure of climate change and human activities, D. spathacea has become endangered in China. Moreover, misidentification between D. spathacea and its terrestrial relative D. cauda-felina poses further challenges to field protection and proper medicinal usage of D. spathacea. Thus, to address these problems, we sequenced and assembled mitochondrial (mt) and chloroplast (cp) genomes for both D. spathacea and D. cauda-felina. Comparative analysis revealed apparently different size and scaffold number between the two mt genomes, but a high similarity between the cp genomes. Eight regions with high sequence divergence were identified between the two cp genomes, which might be used for developing candidate DNA markers for distinguishing the two species. The splitting between D. spathacea and D. cauda-felina was inferred to occur at ~6.8 - 7.7 million years ago (Mya), which may be driven by the environment fluctuations in late Miocene. In the cp genome, 12 genes related to the expression of photosynthesis-associated proteins were detected with signatures of positive selection, which may contribute to the origin and evolutionary adaptation of Dolichandrone mangrove species. These new findings do not only enrich organelle genomic resources of Dolichandrone species, but also provide important genetic clues for improving the conservation and proper usage of endangered mangrove associate D. spathacea.

Unveiling the analgesic and antipyretic drug acetaminophen catabolic mechanism in Pseudomonas taiwanensis AP-1.

Acetaminophen (APAP), an analgesic and antipyretic drug, is commonly detected in wastewater treatment plant (WWTP) effluents, surface water, and soil, indicating its status as an emerging environmental contaminant. In this study, we isolated a bacterium, Pseudomonas taiwanensis AP-1, capable of completely mineralizing APAP and utilizing it as the sole carbon source for growth. A newly identified metabolite, γ-glutamyl-4-aminophenol (γ-G4AP), was reported for the first time in the degradation of APAP by strain AP-1. Two amidases (ApaH1 and ApaH2), responsible for the conversion of APAP to 4-aminophenol (4-AP), were identified through a combination of genomic comparison, heterologous expression, and gene knockout. Notably, ApaH1 played a pivotal role in the degradation of APAP by strain AP-1. The catalytic triad of ApaH1 (K82-S161-S185) and ApaH2 (K85-S160-S184) were identified as by molecular docking and site-directed mutagenesis. Additionally, a gene cluster apd for the metabolism of 4-AP was also successfully identified in strain AP-1, consisting of the aniline dioxygenase gene cluster apdBCD1D2EF and the BT catabolic gene apdGH. Interestingly, the 4-AP metabolic gene cluster apd was highly conserved among other Pseudomonas strains capable of APAP degradation. Our results provide new insights into the mechanism of APAP biodegradation and strain AP-1 may be a promising bacterium for the bioremediation of APAP pollutions.

No prognostic impact of staging bone scan in patients with stage IA non-small cell lung cancer.

OBJECTIVE: To investigate the survival benefit of preoperative bone scan in asymptomatic patients with early-stage non-small cell lung cancer (NSCLC). METHODS: This retrospective study included patients with radical resection for stage T1N0M0 NSCLC between March 2013 and December 2018. During postoperative follow-up, we monitored patient survival and the development of bone metastasis. We compared overall survival, bone metastasis-free survival, and recurrence-free survival in patients with or without preoperative bone scan. Propensity score matching and inverse probability of treatment weighting were used to minimize election bias. RESULTS: A total of 868 patients (58.19 ± 9.69 years; 415 men) were included in the study. Of 87.7% (761 of 868) underwent preoperative bone scan. In the multivariable analyses, bone scan did not improve overall survival (hazard ratio [HR] 1.49; 95% confidence intervals [CI] 0.91-2.42; p = 0.113), bone metastasis-free survival (HR 1.18; 95% CI 0.73-1.90; p = 0.551), and recurrence-free survival (HR 0.89; 95% CI 0.58-1.39; p = 0.618). Similar results were obtained after propensity score matching (overall survival [HR 1.28; 95% CI 0.74-2.23; p = 0.379], bone metastasis-free survival [HR 1.00; 95% CI 0.58-1.72; p = 0.997], and recurrence-free survival [HR 0.76; 95% CI 0.46-1.24; p = 0.270]) and inverse probability of treatment weighting. CONCLUSION: There were no significant differences in overall survival, bone metastasis-free survival, and recurrence-free survival between asymptomatic patients with clinical stage IA NSCLC with or without preoperative bone scan.

Quantitative proteomics of the miR-301a/SOCS3/STAT3 axis reveals underlying autism and anxiety-like behavior.

Autism is a widespread neurodevelopmental disorder. Although the research on autism spectrum disorders has been increasing in the past decade, there is still no specific answer to its mechanism of action and treatment. As a pro-inflammatory microRNA, miR-301a is abnormally expressed in various psychiatric diseases including autism. Here, we show that miR-301a deletion and inhibition exhibited two distinct abnormal behavioral phenotypes in mice. We observed that miR-301a deletion in mice impaired learning/memory, and enhanced anxiety. On the contrary, miR-301a inhibition effectively reduced the maternal immune activation (MIA)-induced autism-like behaviors in mice. We further demonstrated that miR-301a bound to the 3'UTR region of the SOCS3, and that inhibition of miR-301a led to the upregulation of SOCS3 in hippocampus. The last result in the reduction of the inflammatory response by inhibiting phosphorylation of AKT and STAT3, and the expression level of IL-17A in poly(I:C)-induced autism-like features in mice. The obtained data revealed the miR-301a as a critical participant in partial behavior phenotypes, which may exhibit a divergent role between gene knockout and knockdown. Our findings ascertain that miR-301a negatively regulates SOCS3 in MIA-induced autism in mice and could present a new therapeutic target for ameliorating the behavioral abnormalities of autism.

Bidirectional association between perioperative skeletal muscle and subcutaneous fat in colorectal cancer patients and their prognostic significance.

Introduction: Low skeletal muscle mass and high adipose tissue coexist across the body weight spectrum and independently predict the survival ratio of colorectal cancer (CRC) patients. This combination may lead to a mutually exacerbating vicious cycle. Tumor-associated metabolic conditions primarily affect subcutaneous adipose tissue, but the nature and direction of its relationship with skeletal muscle are unclear. This study aims to examine the bidirectional causal relationship between skeletal muscle index (SMI) and subcutaneous fat index (SFI) during the perioperative period in CRC patients; as well as to validate the association between perioperative SMI, SFI, and CRC prognosis. Methods: This population-based retrospective cohort study included patients with stage I-III colorectal cancer who underwent radical resection at the Third Affiliated Hospital of Kunming Medical University between September 2012 and February 2019. Based on inclusion and exclusion criteria, 1,448 patients were analyzed. Preoperative (P1), 2 months postoperative (P2), and 5 months postoperative (P3) CT scans were collected to evaluate the skeletal muscle index (SMI; muscle area at the third lumbar vertebra divided by height squared) and subcutaneous fat index (SFI; subcutaneous fat area at the third lumbar vertebra divided by height squared). A random intercept cross-lagged panel model (RI-CLPM) was used to examine the intra-individual relationship between SMI and SFI, and Cox regression was employed to assess the association between SMI, SFI, recurrence-free survival (RFS), and overall survival (OS). Results: The median age at diagnosis was 59.00 years (IQR: 51.00-66.00), and 587 patients (40.54%) were female. RI-CLPM analysis revealed a negative correlation between SFI and subsequent SMI at the individual level: P1-P2 (ß = -0.372, p = 0.038) and P2-P3 (ß = -0.363, p = 0.001). SMI and SFI showed a negative correlation during P1-P2 (ß = -0.363, p = 0.001) but a positive correlation during P2-P3 (ß = 0.357, p = 0.006). No significant correlation was found between the random intercepts of SFI and SMI at the between-person level (r = 0.157, p = 0.603). The Cox proportional hazards multivariate regression model identified that patients with elevated SFI had poorer recurrence-free survival (HR, 1.24; 95% CI: 1.00-1.55). Compared to patients with normal preoperative SMI and SFI, those with low SMI or high SFI had poorer recurrence-free survival (HR, 1.26; 95% CI: 1.03-1.55) and overall survival (HR, 1.39; 95% CI: 1.04-1.87). However, no significant association between SMI and SFI and the prognosis of colorectal cancer patients was observed postoperatively. Conclusion: In CRC patients, preoperative muscle loss leads to postoperative fat accumulation, exacerbating muscle loss in a feedback loop. Elevated preoperative SFI predicts poorer survival outcomes. Monitoring SMI and SFI is crucial as prognostic indicators, despite non-significant postoperative associations. Further research is needed to improve patient outcomes.

Study of peripheral blood inflammatory factor levels and their clinical value in patients with lupus nephritis.

OBJECTIVE: To explore the effect of traditional Chinese and western medicine on the levels of inflammatory cytokines in the peripheral blood of patients with lupus nephritis (LN). METHODS: A total of 80 patients with LN admitted to the hospital from August 2016 to August 2017 were retrospectively analyzed. They were equally separated into an experimental group and a control group by the different types of medications. The control group was treated with western medicine, and the experimental group was treated with the combination of traditional Chinese and western medicines. The therapeutic effects were compared. RESULTS: The levels of IL-6, IL-18 and TNF-α in the experimental group after treatment were (5.47±1.66) pg/ml, (31.66±3.87) pg/ml, and (9.28±3.06) pg/ml, respectively, which were significantly lower than (13.71±3.86) pg/ml, (68.47±4.26) pg/ml, and (22.17±6.54) pg/ml before treatment. The difference was statistically significant (t1 = 12.403, t2 = 40.450, t3 = 11.291, all P<0.001). In the control group after treatment, the levels of IL-6, IL-18 and TNF-α were (12.68±1.32) pg/ml, (68.22±3.42) pg/ml, and (19.78±5.57) pg/ml, respectively. The difference in control and experimental groups was statistically significant (t1 = 21.501, t2 = 44.771, t3 = 10.449, P<0.001). The total effective rate was 95.00% (38/40) in the experimental group and 80.00% (32/40) in control group, (X2 = 4.114, P<0.001). There SLEDAI scores of the experimental group were much lower than control after 8 and 12 weeks of treatment (t1 = 8.186, t2 = 20.776, P<0.001). Moreover, the liver and kidney Yin deficiency symptoms in both groups were significantly improved after treatment (P<0.01). CONCLUSION: The combined treatment of traditional Chinese and western medicine can successfully prevent the secretion of serum IL-6, IL-18 and TNF-α, control the development of disease, boost the therapeutic outcome, and alleviate the immune injury of the body.

Effect evaluation of traffic guidance in urban underground road diverging and merging areas: A simulator study.

Traffic accidents occur frequently in urban underground road diverging and merging areas due to the limited vision and complex traffic. Well-designed traffic visual guidance is one of the effective measures to alleviate the traffic safety problems in the diverging and merging areas of urban underground roads. In this study, four different integrated traffic guidance schemes (including signs, marking lines and sidewall guidance) were proposed and their effects on drivers' behaviour were investigated through driving simulator experiments and questionnaire survey. To investigate the influence of different schemes, eight variables about driving behaviour and guidance efficiency were assessed for analysis. Finally, a fuzzy comprehensive evaluation model based on analytic hierarchy process (FCE + AHP) was constructed to evaluate the effect of guidance schemes. Vehicle running state, driver operation behaviour and guidance efficiency were mainly considered. The guidance evaluation results obtained by the model were consistent with the conclusions of the driver subjective questionnaire. The results show that reasonable setting of white dotted lines and colour guidance can help drivers find exits quickly and improve driving stability. However, excessive combination of traffic guidance leads to information overload and produces the opposite effect. This study can provide a generic framework for the design and evaluation of traffic guidance facilities of urban underground roads.

Insight into structural characteristics of theabrownin from Pingwu Fuzhuan brick tea and its hypolipidemic activity based on the in vivo zebrafish and in vitro lipid digestion and absorption models.

Fuzhuan brick tea (FBT) is a post-fermented dark tea preferred by consumers for its excellent hypolipidemic activity, and theabrownin (TB) is the main bioactive composition in FBT. This work explored the structural and hypolipidemic properties of TB derived from Pingwu FBT, and investigated whether it exerted hypolipidemic activity by inhibiting intestinal lipid absorption. Structural characterization revealed that TB was an amorphous polymerized phenolic compound rich in hydroxyl and carboxyl groups with good thermostability. In vivo, TB and its fractions with different molecular weights (TB-LT3k, TB-3-10k, TB-10-30k, TB-30-100k, TB-GT100k) significantly reduced the lipid levels of hyperlipidemia zebrafish (P < 0.05). Moreover, TB attenuated hyperlipidemia by inhibiting intestinal lipid absorption, as TB effectively bound to bile acids, inhibited enzymatic activity of pancreatic lipase and cholesterol esterase, influenced micelle formation, and decreased micellar cholesterol solubility. Results facilitated research on TB and offered support for its feasibility as a natural alternative to prevent hyperlipidemia.

The Effect of TLR9, MyD88, and NF-κB p65 in Systemic Lupus Erythematosus.

Purpose: This study was conducted to characterize the expression level of peripheral blood toll-like receptors 9 (TLR9), nuclear factor kappa-B protein 65 (NF-κB p65), and myeloid differentiation factor88 (MyD88) of active systemic lupus erythematosus (SLE) and analyse their clinical significance. Methods: The prospective cohort study enrolled 30 active SLE patients (SG1 group), 30 stable SLE patients (SG2 group), and 20 healthy individuals (RG group) in the First Affiliated Hospital of Hainan Medical University between January 2018 and June 2020. All SLE patients were treated with methylprednisolone tablets. Quantitative polymerase chain reaction (qPCR) was used to determine the levels of TLR9, MyD88, and NF-κB p65 in the peripheral blood mononuclear cell (PBMC). ELISA was adopted for the determination of serum interleukin (IL-6) and tumor necrosis factor-α (TNF-α). Results: Patients in SG1 showed the highest mRNA levels of TLR9, MyD88, and NF-κB p65, followed by SG2, and then RG. SG1 had the highest serum levels of IL-6 and TNF-α, followed by SG2 and RG. The level of TLR9 was positively correlated with the SLE disease activity index (SLEDAI) and negatively correlated with complement component 3 (C3) and complement component 4 (C4). MyD88 and NF-κB p65 were positively correlated with SLEDAI. Conclusion: Compared with a healthy status, SLE induces an increase in TLR9, MyD88, NF-κB p65, IL-6, and TNF-α levels, and the activation of the TLR9-MyD88-NF-κB p65 signal path was associated with the pathogenesis of SLE.