Position- and region-isomerized derivatives of a V-shaped fluorophore: the unique solution-state dual emission and the unusual force-induced solid-state turn-on emission.

A V-shaped parent fluorophore as well as its position- and region-isomerized derivatives with a phenyl introduced on either the electron-donating or the electron-withdrawing moiety in the ortho-, meta- or para-linkage is prepared. Compared with the parent, these derivatives exhibit unique solvent-dependent dual emission in solutions presumably due to the considerably enhanced rotation energy barrier triggered by the insertion of the phenyl, which results in competitive relaxation between the LE and the TICT states. The intrinsically differentiated electron effect induced by the linkage position, which is strengthened by the twisted conformations, should be responsible for the faint or fully quenched fluorescence of the ortho- and meta-isomers in both solution and solid states. The rare turn-on solid-state emission of such isomers under force stimuli is caused by the enhanced π-conjugation effect on excited molecules, which are released from broken lattices to possess more planarized geometries. Moreover, the red shifts of emission wavelengths before and after force application are remarkably reduced from the parent to the derivatives. X-ray crystallography helps us gain a deep insight on the reasons for such a reduction.

Impact of gum chewing on the quality of bowel preparation for colonoscopy: an endoscopist-blinded, randomized controlled trial.

BACKGROUND AND AIMS: Gum chewing can accelerate motility in the GI tract; clinical studies suggested gum chewing can reduce postoperative ileus. However, no trial has investigated the effect of gum chewing on bowel preparation for colonoscopy in addition to polyethylene glycol (PEG). The objective of this study was to investigate whether gum chewing before colonoscopy can increase the quality of bowel preparation. METHODS: This was a single-center, randomized controlled trial. Consecutive patients undergoing colonoscopy were randomized to the gum group or the control group. Patients in the gum group chewed sugar-free gum every 2 hours for 20 minutes each time from the end of drinking 2 L of PEG to the beginning of colonoscopy. Patients in the control group only received 2 L of PEG before colonoscopy. The quality of bowel preparation, procedure time, adenoma detection rate, patients' tolerance, and adverse events were compared. RESULTS: Three hundred patients were included in the study (150 in the control group, 150 in the gum group). More than 90% of patients in both groups were satisfied with the process of bowel preparation, and the incidence of adverse events was comparable in the 2 groups (41.3% vs 46.0%, P = .42). The mean Boston Bowel Preparation Scale score was 6.2 ± 1.4 and 6.1 ± 1.2 in the control group and the gum group, respectively, and the difference between the 2 groups was not significant (P = .51). CONCLUSIONS: This study indicates that gum chewing does not improve the quality of bowel preparation for colonoscopy, but it can improve patients' satisfaction with the process of bowel preparation and does not have negative effects on cleanliness. (Clinical trials registration number: NCT02507037.).

Emission behaviours of novel V- and X-shaped fluorophores in response to pH and force stimuli.

A family of novel fluorophores with V- and X-shaped skeletons is rationally designed and prepared. Due to the extended cross π-conjugation in the X-shaped ones, their emission wavelengths in both solution and the solid state exhibit considerable bathochromic shifts compared with those of the V-shaped ones. It is found that a heavy intramolecular charge transfer (ICT) effect is the primary element for the mechanofluorochromic (MFC) response of this family, and an appropriate crystallinity of the sample is also indispensible for it to be MFC-active. Additionally, most fluorophores in this family are responsive to pH stimuli and display diverse and reversible changes of emission features. Interestingly, a V-shaped fluorophore exhibits a unique size-dependent emission behaviour, which makes it a distinctive three-color emitter.

Dual role of leukotriene B4 receptor type 1 in experimental sepsis.

BACKGROUND: The controversial results from different studies suggested that leukocyte recruitment mediated by leukotriene B4 (LTB4) and its receptor might improve pathogen clearance, but might also aggravate organ injury during sepsis. The present study was performed to compare the effect of BLT1 ligand LTB4 and its antagonist U-75302 on the development of sepsis. METHODS: Sepsis in mice was induced by cecal ligation and puncture (CLP). The mice were allocated into sham group, CLP group, U-75302 group, and LTB4 group. In the latter three groups, CLP mice were treated by intraperitoneal saline, U-75302, and LTB4, respectively. Their effect on the progression of sepsis were compared by histopathologic tests, level of systemic cytokines, counts of immune cells and bacterial clearance, and survival rate. RESULTS: The histopathologic tests showed that U-75302 attenuated lung injury, whereas LTB4 aggravated liver injury. LTB4 increased the plasma levels of interleukin-6, tumor necrosis factor-α, and U-75302 increased the level of plasma interleukin-10. LTB4 increased whereas U-75302 reduced the neutrophil numbers in the peritoneal lavage fluid. LTB4 also increased the number of peritoneal and splenic CD4(+) and CD8(+) T cells. Bacterial clearance in blood and peritoneal lavage fluid was significantly enhanced in the LTB4 group. Both U-75302 and LTB4 did not change the survival rate significantly compared with vehicle, but mortality in the LTB4 group was significantly higher than in the U-75302 group. Dose response analyses were also performed to compare the effect of U-75302 and LTB4 at different doses. Different doses of both agents did not influence the survival rate of CLP mice. CONCLUSIONS: U-75302 attenuates sepsis-induced organ injury, whereas LTB4 increases the leukocyte recruitment toward infection site, but LTB4 showed a more lethal effect than U-75302 during polymicrobial sepsis.

Selenium represses microRNA-202-5p/MICU1 aixs to attenuate mercuric chloride-induced kidney ferroptosis.

Mercuric chloride (HgCl2) is a nephrotoxic contaminant that is widely present in the environment. Selenium (Se) can effectively antagonize the biological toxicity caused by heavy metals. Here, in vivo and in vitro models of Se antagonism to HgCl2-induced nephrotoxicity in chickens were established, with the aim of exploring the specific mechanism. Morphological observation and kidney function analysis showed that Se alleviated HgCl2-induced kidney tissue injury and cytotoxicity. The results showed that ferroptosis was the primary mechanism for the toxicity of HgCl2, as indicated by iron overload and lipid peroxidation. On the one hand, Se significantly prevented HgCl2-induced iron overload. On the other hand, Se alleviated the intracellular reactive oxygen species (ROS) levels caused by HgCl2. Subsequently, we focused on the sources of ROS during HgCl2-induced ferroptosis. Mechanically, Se reduced ROS overproduction induced by HgCl2 through mitochondrial calcium uniporter (MCU)/mitochondrial calcium uptake 1 (MICU1)-mediated mitochondrial calcium ion (Ca2+) overload. Furthermore, a dual luciferase reporter assay demonstrated that MICU1 was the direct target of miR-202-5p. Overall, Se represses miR-202-5p/MICU1 axis to attenuate HgCl2-induced kidney ferroptosis.

Selenium alleviates pancreatic fibrosis in chickens caused by mercuric chloride: Involvement of the MAPK signaling pathway and selenoproteins.

Mercuric chloride (HgCl2) is a widespread inorganic mercury with digestive toxicity. The pancreas is an important digestive organ in animals, and pancreatic fibrosis (PF) is a major pathological feature of chronic pancreatitis, which can be caused by heavy metals. Selenium (Se) is an essential trace element for the animal organism, performing biological functions in the form of selenoproteins, as well as alleviating the toxicity of heavy metals. In this study, we explored the specific mechanisms underlying the protective effect of Se on HgCl2-induced pancreatic injury in chickens. Morphological observation and serum biochemical analysis showed that Se attenuated HgCl2-caused pancreatic tissue damage and elevated glucose concentration and α-amylase activity. Next, the expression of oxidative stress indicators such as MDA and GSH-Px as well as inflammation-related markers including IL-1ß, IL-6, and TNF-α were detected. Results showed that Se had an inhibitory effect on HgCl2-induced oxidative stress and inflammation. Furthermore, we found that Se alleviated HgCl2-induced PF by detecting the expression of markers related to PF including TGF-ß1, α-SMA, COL1A1, and FN1. Mechanistically, Se attenuated HgCl2-induced PF via the MAPK signaling pathway. Importantly, several selenoproteins, especially those with antioxidant activity, were involved in the protective effect of Se on HgCl2 toxicity. In conclusion, our findings demonstrated that Se inhibited HgCl2-induced oxidative stress and inflammation and alleviated chicken PF through the MAPK signaling pathway, in which some antioxidant selenoproteins were involved.

Dietary Iron Overload Triggers Hepatic Metabolic Disorders and Inflammation in Laying Hen.

Iron, an essential trace element, is involved in various physiological processes; however, consumption of excessive iron possesses detrimental effects. In practical feed production, the iron content added to feeds often far exceeds the actual demand, resulting in an excess of iron in the body. The liver as a central regulator of iron homeostasis is susceptible to damage caused by disorders in iron metabolism. A model of hepatic iron overload in laying hens was developed in this study by incorporating iron into their diet, and the specific mechanisms underlying iron overload-induced hepatic injury were investigated. Firstly, this study revealed that a high-iron diet resulted in hepatic iron overload, accompanied by impaired liver function. Next, assessment of oxidative stress markers indicated a decrease in activities of T-SOD and CAT, coupled with an increase in MDA content, pointing to the iron-overloaded liver oxidative stress. Thirdly, the impact of iron overload on hepatic glycolipid and bile acid metabolism-related gene expressions were explored, including PPAR-α, GLUT2, and CYP7A1, highlighting disruptions in hepatic metabolism. Subsequently, analyses of inflammation-related genes such as iNOS and IL-1ß at both protein and mRNA levels demonstrated the presence of inflammation in the liver under conditions of dietary iron overload. Overall, this study provided comprehensive evidence that dietary iron overload contributed to disorders in glycolipid and bile acid metabolism, accompanied by inflammatory responses in laying hens. Further detailing the specific pathways involved and the implications of these findings could offer valuable insights for future research and practical applications in poultry nutrition.

miR-15b-5p promotes HgCl2-induced chicken embryo kidney cells ferroptosis by targeting ß-TrCP-mediated ATF4 ubiquitin degradation.

Mercuric chloride (HgCl2), a widespread environmental pollutant, induces ferroptosis in chicken embryonic kidney (CEK) cells. Whereas activating transcription factor 4 (ATF4), a critical mediator of oxidative homeostasis, plays a dual role in ferroptosis, but its precise mechanisms in HgCl2-induced ferroptosis remain elusive. This study aims to investigate the function and molecular mechanism of ATF4 in HgCl2-induced ferroptosis. Our results revealed that ATF4 was downregulated during HgCl2-induced ferroptosis in CEK cells. Surprisingly, HgCl2 exposure has no significant impact on ATF4 mRNA level. Further investigation indicated that HgCl2 enhanced the expression of the E3 ligase beta-transducin repeat-containing protein (ß-TrCP) and increased ATF4 ubiquitination. Subsequent findings identified that miR-15b-5p as an upstream modulator of ß-TrCP, with miR-15b-5p downregulation observed in HgCl2-exposed CEK cells. Importantly, miR-15b-5p mimics suppressed ß-TrCP expression and reversed HgCl2-induced cellular ferroptosis. Mechanistically, HgCl2 inhibited miR-15b-5p, and promoted ß-TrCP-mediated ubiquitin degradation of ATF4, thereby inhibited the expression of antioxidant-related target genes and promoted ferroptosis. In conclusion, our study highlighted the crucial role of the miR-15b-5p/ß-TrCP/ATF4 axis in HgCl2-induced nephrotoxicity, offering a new therapeutic target for understanding the mechanism of HgCl2 nephrotoxicity.

Clinicopathological Features of Sessile Serrated Polyps in China: A Retrospective Study of a Tertiary Hospital.

BACKGROUND: Serrated polyps have been recognized as the important premalignant lesions. In this study, we aimed to analyze the clinicopathological features of sessile serrated polyps and determine the association between sessile serrated polyps and synchronous advanced adenomas. METHODS: Consecutive patients undergoing diagnostic or therapeutic colonoscopies (including 156 681 diagnostic colonoscopies) from 2011 to 2019 were included. RESULTS: A total of 958 patients, including 699 (73%) males, were detected with at least 1 sessile serrated polyp, and 65.9% (n = 658) of sessile serrated polyps were located in the distal colon. Advanced serrated lesions accounted for 9.1% (n = 91) of all the sessile serrated polyp (n = 999). The types of SSP included flat type (953/999, 95.4%) and sub-pedunculated or pedunculated type (46/999, 4.6%). Meanwhile, there was no obvious evidence supporting the association between advanced adenomas and characteristics of advanced serrated lesions or sessile serrated polyps. CONCLUSION: Sessile serrated polyps seem to be more frequently seen in the distal colon of men in this study. However, more evidence is required to confirm the actual distribution of sessile serrated polyp in colon among Chinese people. There is still much room for improvement of sessile serrated polyp detection rate, and more importance should be attached to sessile serrated polyp both for pathologists and endoscopists.

Selenoprotein K knockdown induces apoptosis in skeletal muscle satellite cells via calcium dyshomeostasis-mediated endoplasmic reticulum stress.

Skeletal muscle satellite cells (SMSCs), known as muscle stem cells, play an important role in muscle embryonic development, post-birth growth, and regeneration after injury. Selenoprotein K (SELENOK), an endoplasmic reticulum (ER) resident selenoprotein, is known to regulate calcium ion (Ca2+) flux and ER stress (ERS). SELENOK deficiency is involved in dietary selenium deficiency-induced muscle injury, but the regulatory mechanisms of SELENOK in SMSCs development remain poorly explored in chicken. Here, we established a SELENOK deficient model to explore the role of SELENOK in SMSCs. SELENOK knockdown inhibited SMSCs proliferation and differentiation by regulating the protein levels of paired box 7 (Pax7), myogenic factor 5 (Myf5), CyclinD1, myogenic differentiation (MyoD), and Myf6. Further analysis exhibited that SELENOK knockdown markedly activated the ERS signaling pathways, which ultimately induced apoptosis in SMSCs. SELENOK knockdown-induced ERS is related with ER Ca2+ ([Ca2+]ER) overload via decreasing the protein levels of STIM2, Orai1, palmitoylation of inositol 1,4,5-trisphosphate receptor 1 (IP3R1), phospholamban (PLN), and plasma membrane Ca2+-ATPase (PMCA) while increasing the protein levels of sarco/endoplasmic Ca2+-ATPase 1 (SERCA1) and Na+/Ca2+ exchanger 1 (NCX1). Moreover, thimerosal, an activator of IP3R1, reversed the overload of [Ca2+]ER, ERS, and subsequent apoptosis caused by SELENOK knockdown. These findings indicated that SELENOK knockdown triggered ERS driven by intracellular Ca2+ dyshomeostasis and further induced apoptosis, which ultimately inhibited SMSCs proliferation and differentiation.

Effect and safety of probiotics for treating urticaria: A systematic review and meta-analysis.

BACKGROUND: To assess the effect and safety of probiotics for treating urticaria. METHODS: Randomized controlled trial (RCT) papers on the probiotics treatment published before May 2019 were retrieved from various databases like PubMed, EMbase, MEDLINE (Ovid), SCI-Hub, Springer, ClinicalKey, VIP, and CNKI. The treatment plan that we include are oral administration of single probiotic, multiple probiotics, and the combination of probiotics and antihistamines. Meta-analysis of the data was performed by RevMan 5.3 software. RESULTS: A total of nine RCT papers were included: four papers for oral administration of single probiotic, three papers for oral administration of multiple probiotics, and two papers for oral administration of a probiotic combined with antihistamines. The results of meta-analysis showed that the therapeutic effect of the probiotic group was significantly higher than the control group (placebo or antihistamines) (RR = 1.09, 95% CI: 1.03-1.16, p = 0.006). And compared with the placebo group, the therapeutic effect of single probiotic group was significantly improved (RR = 1.11, 95% CI: 1.01-1.21, p = 0.03). Regarding therapeutic effect, there was no statistically significant difference between the multiple probiotics group and placebo group (RR = 1.00, 95% CI: 0.94 ~ 1.07, p = 0.91); the therapeutic effect of single probiotic combined antihistamine group was significantly higher than the antihistamine group (RR = 1.13, 95% CI: 1.07-1.19, p < 0.0001). Regarding the incidence of adverse reactions, there was no significant difference between the probiotic group and the control group (p = 0.46). CONCLUSION: The treatment plan of oral administration of probiotics has significant therapeutic effects on urticaria, but the therapeutic effects of the administration of multiple probiotics and the safety of probiotic therapy are still not yet obvious. Some large-scale, multi-centered RCT studies are needed in the future for clarification.

Prognostic and Predictive Value of BGN in Colon Cancer Outcomes and Response to Immunotherapy.

BACKGROUND: Colon cancer is one of the most frequent malignancies and causes high mortality worldwide. Exploring the tumor-immune interactions in the tumor microenvironment and identifying new prognostic and therapeutic biomarkers will assist in decoding the novel mechanism of tumor immunotherapy. BGN is a typical extracellular matrix protein that was previously validated as a signaling molecule regulating multiple processes of tumorigenesis. However, its role in tumor immunity requires further investigation. METHODS: The differentially expressed genes in three GEO datasets were analyzed, and BGN was identified as the target gene by intersection analysis of PPIs. The relevance between clinical outcomes and BGN expression levels was evaluated using data from the GEO database, TCGA and tissue microarray of colon cancer samples. Univariable and multivariable Cox regression models were conducted for identifying the risk factors correlated with clinical prognosis of colon cancer patients. Next, the association between BGN expression levels and the infiltration of immune cells as well as the process of the immune response was analyzed. Finally, we predicted the immunotherapeutic response rates in the subgroups of low and high BGN expression by TIS score, ImmuCellAI and TIDE algorithms. RESULTS: BGN expression demonstrated a statistically significant upregulation in colon cancer tissues than in normal tissues. Elevated BGN was associated with shorter overall survival as well as unfavorable clinicopathological features, including tumor size, serosa invasion and length of hospitalization. Mechanistically, pathway enrichment and functional analysis demonstrated that BGN was positively correlated with immune and stromal scores in the TME and primarily involved in the regulation of immune response. Further investigation revealed that BGN was strongly expressed in the immunosuppressive phenotype and tightly associated with the infiltration of multiple immune cells in colon cancer, especially M2 macrophages and induced Tregs. Finally, we demonstrated that high BGN expression presented a better immunotherapeutic response in colon cancer patients. CONCLUSION: BGN is an encouraging predictor of diagnosis, prognosis and immunotherapeutic response in patients with colon cancer. Assessment of BGN expression represents a novel approach with great promise for identifying patients who may potentially benefit from immunotherapy.

Feasibility of using narrow band imaging international colorectal endoscopic classification for diagnosing colorectal neoplasia in China: A multicenter pilot observational study.

OBJECTIVE: We aimed to investigate whether Chinese endoscopists without narrow-band imaging (NBI) experiences could achieve high accuracy in the real-time diagnosis of colorectal polyps using NBI International Colorectal Endoscopic (NICE) classification after web-based training. METHODS: Altogether 15 endoscopists from five centers with no NBI experiences followed a short, web-based training program on the NICE classification and took web-based test. Their performances were compared with 15 matched experienced endoscopists with no NBI experience who received no NBI training. These 15 trained endoscopists then made real-time diagnoses of colorectal neoplasia. A logistic regression was used to assess potential predictors of diagnostic performance. RESULTS: Compared with those who received no training, trained endoscopists achieved comparable overall accuracy (85.3% vs 83.1%, P = 0.408) and accuracy at a high-confidence level (87.0% vs 86.0%, P = 0.670), but had a higher confidence rate (86.1% vs 83.7%, P = 0.004) for the diagnosis of neoplasia. Real-time diagnostic accuracy, sensitivity and specificity were 94.3% (95% confidence interval [CI] 91.5%-96.2%), 96.2% (95% CI 93.4%-97.9%) and 85.3% (95% CI 74.8%-92.1%) at high-confidence level. The high-confidence level was the strongest predictor of real-time diagnostic accuracy (odds ratio 12.66, P < 0.001). CONCLUSIONS: Web-based training can improve the confidence level of endoscopists in accurately diagnosing colorectal polyps using the NICE classification. Chinese endoscopists can achieve high accuracy in diagnosing colorectal neoplasia at a high confidence level (ClinicalTrials ID: NCT02033980).

Quantitative assessment of the effect of position changes during colonoscopy withdrawal.

OBJECTIVE: Although trials assessing the effectiveness of position changes during colonoscopy withdrawal have been reported, there has been no agreement whether such position changes actually improve the polyp detection rate (PDR) or adenoma detection rate (ADR). This article aimed to address this issue by performing a systematic review. METHODS: Relevant studies from databases including PubMed, EMBASE and the Cochrane Library and Science Citation Index were retrieved. Two reviewers independently identified potentially relevant studies. Outcome measures were PDR, ADR and bowel distention. RESULTS: Eight studies were included, of which seven were randomized controlled trials (RCTs). A non-randomized controlled trial and all four cross-over RCTs reported significant improvement in PDR, ADR and bowel distention with position change during colonoscopic withdrawal, while three parallel-group RCTs did not confirm its effectiveness. CONCLUSIONS: The conflicting results of high-quality trials indicate that the effectiveness of position change during colonoscopy withdrawal on PDR, ADR and bowel distension is uncertain. Thus, position change during colonoscopy withdrawal should not be routinely applied until future studies demonstrate its efficacy.

Constipation, fiber intake and non-compliance contribute to inadequate colonoscopy bowel preparation: a prospective cohort study.

OBJECTIVE: Adequate bowel preparation is important for colonoscopy. Currently available evidence on the determinants of poor bowel preparation is largely derived from studies in Western countries. We aimed to identify the risk factors for inadequate bowel preparation for colonoscopy in the Chinese population. METHODS: In this single-center study, patients admitted to the Outpatient Department between March 2013 and December 2015 and had indications for colonoscopy were prospectively enrolled. Questionnaires were administered to the patients. Their characteristics and procedure-related parameters such as procedure time were recorded. Bowel preparation was assessed using Boston bowel preparation scale score. RESULTS: A total of 409 patients with a mean age of 48.8 ± 12.9 years were enrolled in the study, 60.9% of whom were men. On univariate analysis, poor educational level (P = 0.020), chronic constipation (P = 0.001), taking no physical exercise after medication (P < 0.001), a high-fiber diet during the 24-h period immediately preceding the colonoscopy (P < 0.001), incomplete intake of medication (P < 0.001), the passage of yellow or dark stools before colonoscopy (P < 0.001), waiting time (P = 0.001) and stool frequency after medication (P = 0.048) were significantly associated with inadequate bowel preparation. On multivariate analysis, chronic constipation [odds ratio (OR) 2.05, 95% confidence interval (CI) 1.31-3.23, P = 0.002], incomplete intake of the medication (OR 2.77, 95% CI 1.47-5.21, P = 0.002) and a high-fiber diet within 24 h before colonoscopy (OR 2.15, 95% CI 1.40-3.28, P < 0.001) were independent risk factors for inadequate bowel preparation. CONCLUSIONS: Chronic constipation, poor compliance with treatment and high-fiber diet were predictors of poor bowel preparation. Patients with these risk factors require more effective strategies for bowel preparation.