Upregulated Tß4 expression in inflammatory bowel disease impairs the intestinal mucus barrier by inhibiting autophagy in mice.

Disrupted intestinal barrier homeostasis is fundamental to inflammatory bowel disease. Thymosin ß4 (Tß4) improves inflammation and has beneficial effects in dry-eye diseases, but its effects on the intestinal mucus barrier remain unknown. Therefore, this study evaluated the underlying regulatory mechanisms and effects of Tß4 by examining Tß4 expression in a mouse model with dextran sodium sulfate (DSS)-induced colitis and colonic barrier damage. Additionally, we intraperitoneally injected C57BL/6 mice with Tß4 to assess barrier function, microtubule-associated protein 1 light chain 3 (LC3II) protein expression, and autophagy. Finally, normal human colon tissue and colon carcinoma cells (Caco2) were cultured to verify Tß4-induced barrier function and autophagy changes. Mucin2 levels decreased, microbial infiltration increased, and Tß4 expression increased in the colitis mouse model versus the control mice, indicating mucus barrier damage. Moreover, Tß4-treated C57BL/6 mice had damaged intestinal mucus barriers and decreased LC3II levels. Tß4 also inhibited colonic mucin2 production, disrupted tight junctions, and downregulated autophagy; these results were confirmed in Caco2 cells and normal human colon tissue. In summary, Tß4 may be implicated in colitis by compromising the integrity of the intestinal mucus barrier and inhibiting autophagy. Thus, Tß4 could be a new diagnostic marker for intestinal barrier defects.

Causal relationship between gut microbiota and gastrointestinal diseases: a mendelian randomization study.

BACKGROUND: Recent research increasingly highlights a strong correlation between gut microbiota and the risk of gastrointestinal diseases. However, whether this relationship is causal or merely coincidental remains uncertain. To address this, a Mendelian randomization (MR) analysis was undertaken to explore the connections between gut microbiota and prevalent gastrointestinal diseases. METHODS: Genome-wide association study (GWAS) summary statistics for gut microbiota, encompassing a diverse range of 211 taxa (131 genera, 35 families, 20 orders, 16 classes, and 9 phyla), were sourced from the comprehensive MiBioGen study. Genetic associations with 22 gastrointestinal diseases were gathered from the UK Biobank, FinnGen study, and various extensive GWAS studies. MR analysis was meticulously conducted to assess the causal relationship between genetically predicted gut microbiota and these gastrointestinal diseases. To validate the reliability of our findings, sensitivity analyses and tests for heterogeneity were systematically performed. RESULTS: The MR analysis yielded significant evidence for 251 causal relationships between genetically predicted gut microbiota and the risk of gastrointestinal diseases. This included 98 associations with upper gastrointestinal diseases, 81 with lower gastrointestinal diseases, 54 with hepatobiliary diseases, and 18 with pancreatic diseases. Notably, these associations were particularly evident in taxa belonging to the genera Ruminococcus and Eubacterium. Further sensitivity analyses reinforced the robustness of these results. CONCLUSIONS: The findings of this study indicate a potential genetic predisposition linking gut microbiota to gastrointestinal diseases. These insights pave the way for designing future clinical trials focusing on microbiome-related interventions, including the use of microbiome-dependent metabolites, to potentially treat or manage gastrointestinal diseases and their associated risk factors.

Histone deacetylase 9 plays a role in sevoflurane-induced neuronal differentiation inhibition by inactivating cAMP-response element binding protein transcription and inhibiting the expression of neurotrophin-3.

Postoperative cognitive decline (POCD) is a common and serious complication following anesthesia and surgery; however, the precise mechanisms of POCD remain unclear. Our previous research showed that sevoflurane impairs adult hippocampal neurogenesis (AHN) and thus cognitive function in the aged brain by affecting neurotrophin-3 (NT-3) expression; however, the signaling mechanism involved remains unexplored. In this study, we found a dramatic decrease in the proportion of differentiated neurons with increasing concentrations of sevoflurane, and the inhibition of neural stem cell differentiation was partially reversed after the administration of exogenous NT-3. Understanding the molecular underpinnings by which sevoflurane affects NT-3 is key to counteracting cognitive dysfunction. Here, we report that sevoflurane administration for 2 days resulted in upregulation of histone deacetylase 9 (HDAC9) expression, which led to transcriptional inactivation of cAMP-response element binding protein (CREB). Due to the colocalization of HDAC9 and CREB within cells, this may be related to the interaction between HDAC9 and CREB. Anyway, this ultimately led to reduced NT-3 expression and inhibition of neural stem cell differentiation. Furthermore, knockdown of HDAC9 rescued the transcriptional activation of CREB after sevoflurane exposure, while reversing the downregulation of NT-3 expression and inhibition of neural stem cell differentiation. In summary, this study identifies a unique mechanism by which sevoflurane can inhibit CREB transcription through HDAC9, and this process reduces NT-3 levels and ultimately inhibits neuronal differentiation. This finding may reveal a new strategy to prevent sevoflurane-induced neuronal dysfunction.

Comparation of 5 ml and 10 ml Negative Pressures with Wet-suction Techniques for EUS-FNA of Solid Lesions: A Single-center Randomized Controlled Trial.

BACKGROUND AND OBJECTIVES: The negative pressure selectable for the wet-suction technique remains uncertain. The aim was to investigate the quality of sampling and diagnostic accuracy with solid lesions by 5 mL and 10 mL negative pressure with wet-suction techniques. METHODS: This is a single-center, crossover, randomized controlled trial conducted with a random sampling technique. In all, 160 patients consecutively undergoing EUS-FNA for solid lesions were randomized in a ratio of 1:1 into 2 groups, the 5 mL and 10 mL negative pressure wet-suction group. The main outcome was to compare the sample quality between the 2 groups. The secondary outcome was to compare the histologic and cytologic diagnostic accuracy of solid lesions. RESULTS: Pancreatic (n=129) and nonpancreatic (n=27) lesions from 156 lesions were examined. The sample quality concluding cellularity, adequacy, integrity, and blood contamination were comparable between the 2 groups. However, in subgroup analysis, we found 19G FNA provided more integrity of specimen in 5 mL than in 10 mL group (100% vs. 82.9%, P=0.025). In contrast, this benefit was not noteworthy in the 22G FNA subgroup. And there was no statistically significant in histologic (87.82% vs. 87.18%, P=1.000) and cytologic (78.85% vs. 80.77%, P=0.778) accuracy between 5 mL and 10 mL groups. CONCLUSION: When using the wet-suction technique, 5 mL and 10 mL negative pressure offer equivalent sample quality and diagnostic accuracy. However, the 19G FNA can obtain better sample quality with 5 mL negative pressure than 10 mL negative pressure.

Efficacy and safety of potassium-competitive acid inhibitors in the treatment of gastroesophageal reflux: a systematic review and meta-analysis.

BACKGROUND: Gastroesophageal reflux disease (GERD) is a common disease caused by reflux of gastric contents to the esophagus. Proton-pump inhibitors (PPIs) are recommended as a first-line therapy to treat GERD. Recently, the potassium-competitive acid inhibitors have been increasingly in use in clinical practice. We aimed to evaluate the efficacy and safety of P-CABs in GERD. METHODS: We searched PubMed, the Cochrane Library, EMBASE and Web Of Science for publications regarding randomized controlled trials comparing potassium-competitive acid inhibitors to PPI monotherapy or Placebo with respect to efficacy and safety in GERD (until April 2023). The primary outcome was an absence or global symptom improvement and the incidence of adverse events in GERD. The quality of the included literature was assessed using the bias assessment tool recommended in the Cochrane Systematic Assessor's Handbook 5.1.0. We use RevMan 5.3 software for Meta-analysis, sensitivity analysis and publication bias analysis. RESULTS: Of the 991 screened studies, 14 studies including 4868 participants were analyzed. The ORs for the healing rates of GERD with P-CABs versus PPI/Placebo were 2.10 (95% confidence interval [CI] 1.53-2.88), additionally, 1.09 (95% CI 1.05-1.14), 1.03 (95% CI 1.00-1.06) and 1.03 (95% CI 0.99-1.06) in Weeks 2, 4, and 8, respectively. The effectiveness rate of the experimental group was significantly higher than that of the control group (RR 1.73; 95% CI 1.27-2.36). The overall OR of Incidence of adverse events with P-CABs versus PPI/Placebo was 1.08 (95% CI 0.88-1.12). Overall, the risk of bias was low to some concerns. Furthermore, sensitivity analyses confirmed the robustness of the study's conclusion. CONCLUSIONS: Our findings suggest that potassium-competitive acid inhibitors is non-inferior to PPIs as therapy for patients with GERD. The safety outcomes for potassium-competitive acid inhibitors are similar to those for PPIs.

Nutritional screening and assessment tools for patients with cirrhosis based on the Global Leadership Initiative on Malnutrition criteria.

BACKGROUND: Malnutrition is highly prevalent and associated with complications and mortality in patients with cirrhosis. METHODS: This was a prospective observational study. Patients with cirrhosis were screened using the Nutritional Risk Screening 2002, the Royal Free Hospital-Nutritional Prioritizing Tool and the Skeletal Muscle Index. Then, the sensitivity, specificity, positive and negative predictive values, and consistency with the Global Leadership Initiative on Malnutrition criteria results were calculated. We also analysed the association between nutritional status and short-term prognosis. RESULTS: We enrolled 125 patients with cirrhosis, of whom 59.20% and 60.00% were malnourished based on the Global Leadership Initiative on Malnutrition criteria and Skeletal Muscle Index. Some 53.60% and 65.60%, respectively, were classified medium-to-high nutritional risk by Nutritional Risk Screening 2002 and the Royal Free Hospital-Nutritional Prioritizing Tool. The Royal Free Hospital-Nutritional Prioritizing Tool had the best predictive value, and it was more sensitive and had a better negative predictive value than the Nutritional Risk Screening 2002 Tool. The Skeletal Muscle Index also had good sensitivity and predictive value. The Royal Free Hospital-Nutritional Prioritizing Tool, Skeletal Muscle Index and Global Leadership Initiative on Malnutrition criteria showed high concordance. The 3- and 6-month mortality rates were significantly higher for patients with moderate-to-high nutritional risk or malnutrition, regardless of the tool. CONCLUSIONS: When assessing cirrhosis with the Global Leadership Initiative on Malnutrition criteria, the Royal Free Hospital-Nutritional Prioritizing Tool is best for nutritional screening and the Skeletal Muscle Index is also a good nutritional assessment tool.

A comprehensive meta-analysis comparing the effectiveness and safety of cold snare polypectomy and hot snare polypectomy in removing colorectal polyps ≤ 10 mm.

OBJECTIVE: The optimal methods for removing polyps remain controversial especially for polyps ≤10mm. We aim to combine the latest evidence to evaluate and compare the effectiveness and safety of cold snare polypectomy (CSP) and hot snare polypectomy (HSP) in the removal of colorectal polyps ≤10mm in size. METHODS: We performed an extensive search across multiple databases, including PubMed, Embase, Cochrane, and Web of Science, with the search period ending in April 2023 for randomized controlled trials comparing the effectiveness and/or safety of CSP and HSP for the removal of ≤10mm colorectal polyps.The final outcomes included complete resection rate, operation time, and postoperative adverse events (including immediate bleeding, delayed bleeding, and perforation) rates. RESULTS: A total of 14 eligible randomized controlled trials were included, involving 7,460 patients and 15,829 polyps. The incidence of immediate bleeding was observed to be more prevalent in CSP in contrast to HSP, and the disparity was statistically notable (OR=2.18, 95% CI: 1.43-3.30, I2=36%, P=0.0003). The incidence of delayed bleeding was observed to be lower in CSP in contrast to HSP, and this difference was statistically significant (OR=0.30, 95% CI: 0.15-0.58, I2=0%, P=0.0003). Procedure time: both the total colonoscopy time and specific polypectomy time were shorter in CSP than in HSP (MD=-5.92, 95% CI: -9.70 to -2.14, I2=96%, P=0.002; MD=-0.56, 95% CI: -0.91 to -0.20, I2=77%, P=0.002). There were no statistically significant differences in complete resection and the polyp retrieval rate between CSP and HSP. CONCLUSION: CSP is as effective and safe as HSP for ≤10mm colorectal polyps, while effectively reducing the risk of delayed bleeding and shortening the procedure time.

Inhibition of adult hippocampal neurogenesis induced by postoperative CD8 + T-cell infiltration is associated with cognitive decline later following surgery in adult mice.

BACKGROUND: Some patients show persistent cognitive decline for weeks, months or even years after surgery, which seriously affects their long-term prognosis and quality of life. However, most previous basic studies have focused mainly on the mechanisms of early postoperative cognitive decline, whereas cognitive decline in the longer term after surgery is less well-understood. The subgranular zone of the dentate gyrus exhibits life-long neurogenesis, supporting hippocampus-dependent learning and memory. MAIN TEXT: The aim of this study was to investigate whether adult hippocampal neurogenesis (AHN) involves in cognitive decline later following surgery and to further explore the roles of CD8 + T lymphocytes infiltrating the hippocampal parenchyma after surgery in this pathological process. Cognitive function was examined in adult mice that underwent laparotomy combined with partial hepatectomy, and the results showed that cognitive decline persisted in mice who underwent surgery during the first postoperative month, even though there was a trend toward continuous improvement over time. Significantly decreased numbers of DCX + cells, BrdU + cells, and BrdU + /DCX + cells were observed on day 8 after surgery, and a significantly decreased number of NeuN + /BrdU + cells was observed on day 28 after surgery, which indicated inhibition of AHN. After surgery, T lymphocytes, the majority of which were CD8 + T cells, infiltrated the hippocampus and secreted Interferon-γ (IFN-γ). Depletion of CD8 + T cells could inhibit the increase of IFN-γ synthesis, improve hippocampal neurogenesis, and improve postoperative cognitive function. Hippocampal microinjection of IFN-γ neutralizing antibody or adeno-associated virus to knock down IFN-γ receptor 1 (IFNGR1) could also partially attenuate the inhibition of AHN and improve postoperative cognitive function. CONCLUSIONS: These results demonstrate that postoperative infiltration of CD8 + T cells into the hippocampus and subsequent secretion of IFN-γ contribute to the inhibition of AHN and cognitive decline later following surgery.

Author Correction: Genetically encoded tags for direct synthesis of EM-visible gold nanoparticles in cells.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Genetically encoded tags for direct synthesis of EM-visible gold nanoparticles in cells.

Genetically encoded tags for single-molecule imaging in electron microscopy (EM) are long-awaited. Here, we report an approach for directly synthesizing EM-visible gold nanoparticles (AuNPs) on cysteine-rich tags for single-molecule visualization in cells. We first uncovered an auto-nucleation suppression mechanism that allows specific synthesis of AuNPs on isolated tags. Next, we exploited this mechanism to develop approaches for single-molecule detection of proteins in prokaryotic cells and achieved an unprecedented labeling efficiency. We then expanded it to more complicated eukaryotic cells and successfully detected the proteins targeted to various organelles, including the membranes of endoplasmic reticulum (ER) and nuclear envelope, ER lumen, nuclear pores, spindle pole bodies and mitochondrial matrices. We further implemented cysteine-rich tag-antibody fusion proteins as new immuno-EM probes. Thus, our approaches should allow biologists to address a wide range of biological questions at the single-molecule level in cellular ultrastructural contexts.

A novel ultra-low-volume regimen combining 1 L polyethylene glycol and linaclotide versus 2 L polyethylene glycol for colonoscopy cleansing in low-risk individuals: a randomized controlled trial.

BACKGROUND AND AIMS: The single dose of 2 L polyethylene glycol (PEG) has shown high cleaning efficacy and tolerability in low-risk patients. However, the dosage of this regimen is still challenging for many patients. We investigated the efficacy and tolerability of a novel ultra-low-volume regimen using 1 L PEG and linaclotide (1 L PEG+L) versus a single dose of 2 L PEG in low-risk patients. METHODS: In this prospective, randomized, observer-blinded, multicenter study, low-risk adult patients scheduled for colonoscopy were enrolled and randomized (1:1) to receive the 1 L PEG+L regimen or the 2 L PEG regimen. The primary outcome was the effectiveness of bowel cleansing according to the Boston Bowel Preparation Scale. Secondary outcomes included cecal intubation rate, cecal insertion time, withdrawal time, polyp detection rate and adenoma detection rate, tolerability, adverse events, and willingness to repeat bowel preparation. The full analysis set (FAS) and per-protocol set (PPS) were used for statistical analyses. RESULTS: A total of 548 patients comprised the FAS, and 522 patients comprised the PPS. Noninferiority on adequate bowel cleansing of 1 L PEG+L vs 2 L PEG was established both in FAS (90.5% vs 91.6%, P = .644) and PPS (90.3% vs 92.4%, P = .390). There were no significant differences regarding the total score and each segment scores of the Boston Bowel Preparation Scale, cecal intubation rate, cecal insertion time, withdrawal time, polyp detection rate, and adenoma detection rate (all, P > .05). However, patients in the 1 L PEG+L group reported less nausea (7.7% vs 17.1%, P < .01) and vomiting (4.0% vs 10.9%, P < .01) and had a higher willingness to repeat bowel preparation (95.2% vs 82.2%, P < .01). CONCLUSIONS: The regimen of 1 L PEG+L was not inferior to 2 L PEG on colon cleansing, with better tolerability and higher willingness to repeat the bowel preparation in a low-risk population. (Clinical trial registration number: ChiCTR2100053273.).

Development and validation of an EUS-based nomogram for prediction of the malignant potential in gastrointestinal stromal tumors.

BACKGROUND: Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors in the gastrointestinal (GI) tract that require different therapeutic interventions according to the malignancy. We aim to develop and validate a EUS (endoscopic ultrasonography)-based nomogram to predict malignant potential in patients with GIST. METHODS: 258 patients with pathological diagnosis of gastric GISTs were enrolled retrospectively in our hospital from June 2015 to October 2020. Patients were randomly divided into the development cohort (DC, n = 179) and the validation cohort (VC, n = 79). We established a nomogram using lasso regression based on DC data. The predictive effectiveness of the nomogram was evaluated by the area under the receiver operating characteristic curve (AUC). Through bootstrapping, a consistency index (C-index) and calibration chart are developed to evaluate the reliability and accuracy of the nomogram. RESULTS: A total of 192 patients with low-malignant potential (very low and low-risk) GISTs and 66 patients with high-malignant potential (intermediate and high-risk) GISTs were included in this study. The nomogram was constructed with the following 6 EUS indicators: ulceration, hemorrhage, tumor shape, irregular border, transverse diameter, and necrosis. Internal and external validation showed that the nomogram had a good ability to predict the malignant potential of GISTs (AUC = 0.881 and 0.908, respectively). The calibration curve shows that the nomogram has a good agreement between predicted and actual probabilities for differentiating GISTs malignancy (C-index = 0.868 and 0.907, respectively). CONCLUSIONS: This study developed and verified a EUS-based nomogram, which can effectively predict the malignant potential of patients with gastric GISTs.

Twenty cases of gastric adenocarcinoma of the fundic gland type.

BACKGROUND: Gastric adenocarcinoma of the fundic gland type is a new subtype of gastric adenocarcinoma. In 2019, the World Health Organization (WHO) listed gastric adenocarcinoma of the fundic gland type (GA-FG) as a new and rare gastric tumour with a low incidence due to the small number of cumulative cases worldwide. Twenty cases of GA-FG found in our centre were retrospectively analysed to improve the diagnostic ability of endoscopy and pathology in this disease. OBJECTIVE: To investigate the clinicopathological features of fundus-derived gastric tumours and to improve the understanding of and diagnostic accuracy of endoscopy for this disease. METHODS: The clinicopathological characteristics of 20 GA-FG cases between 2018 and 2022 were analysed using clinical and follow-up data and endoscopic, immunohistochemical, and pathological morphology characteristics. RESULTS: In all cases, GA-FG was found in the fundus and the body of the stomach. In total, there were 19 patients with 20 lesions, with most of the patients having a single lesion. One patient had multiple lesions, and another patient had complications from signet ring cell carcinoma (SRCC). All lesions occurred in non-atrophic areas, and 10 patients had gastric fundic gland polyps simultaneously. There were 14 cases of gastric fundus adenocarcinoma and 6 cases of acid-secreting adenoma. Fourteen lesions were treated with endoscopic submucosal dissection (ESD), without recurrence or metastasis during the follow up; 6 patients were followed up for observation, 2 of whom showed no lesions after the first biopsy by gastric endoscopy, and 4 of whom showed no significant changes. CONCLUSIONS: The incidence rate for GA-FG lesions may be underestimated due to their benign course. ESD seems to be an adequate treatment for GA-FG. MAIN POINTS: Gastric adenocarcinoma of the fundic gland type (GA-FG) is located in the fundus and body of the stomach. All lesions occur in non-atrophic areas, and almost one-half involve gastric fundus polyps simultaneously. GA-FG lesions typically follow a benign disease course. ESD seems to be an adequate treatment for GA-FG.

Mast cells disrupt the duodenal mucosal integrity: Implications for the mechanisms of barrier dysfunction in functional dyspepsia.

BACKGROUND: Functional dyspepsia (FD) is a common functional gastrointestinal (GI) disorder, but its pathophysiology is poorly understood. Mast cells (MCs) may play a critical role in the development of FD. Therefore, the aim of this study was to investigate the effect of MCs on barrier function, tight junction (TJ) proteins and related signaling pathways. METHODS: The expression of the TJ proteins claudin-8, ZO-1 and occludin in biopsy tissues from seven FD patients and five controls was assessed. Based on the in vivo results, we further investigated the effect of (1) MC degranulation in a coculture model of Caco-2/RBL-2H3 cells and tryptase in Caco-2 monolayers, (2) MC degranulation in the presence or absence of a PAR-2 antagonist and (3) MC degranulation in the presence or absence of an ERK1/2 signaling pathway inhibitor. The epithelial integrity of Caco-2 cell monolayers was assessed by measuring the transepithelial electrical resistance (TEER). The expression of TJ proteins was evaluated by western blotting, QT-PCR and immunostaining. RESULTS: Epithelial claudin-8, ZO-1 and occludin protein expression were significantly reduced in tissues from FD patients compared with controls. MC degranulation and tryptase decreased the TEER and reduced the expression of TJ proteins in Caco-2 cell monolayers. A PAR-2 antagonist and an ERK1/2 signaling pathway inhibitor significantly reduced the effect of MC degranulation on the TEER and TJ protein expression in Caco-2 cell monolayers. CONCLUSIONS: MCs disrupt duodenal barrier function by modulating the levels of TJ proteins, and the PAR-2 and ERK1/2 signaling pathways may mediate the pathogenesis of FD.

A novel strategy to identify candidate diagnostic and prognostic biomarkers for gastric cancer.

BACKGROUND: Gastric cancer (GC) is one of the most common cancer worldwide. It is essential to identify non-invasive diagnostic and prognostic biomarkers of GC. The aim of the present study was to screen candidate biomarkers associated with the pathogenesis and prognosis of GC by a novel strategy. METHODS: The expression level of gene higher in cancer than in adjacent non-cancer tissue was defined as "positive", and the top 5% genes with "positive rate" were filtered out as candidate diagnostic biomarkers in three Gene Expression Omnibus (GEO) datasets. Further, a prognostic risk model was constructed by multivariate Cox regression analysis in GEO dataset and validated in The Cancer Genome Atlas (TCGA). The expression level of candidate biomarkers was determined in serum and serum-derived exosomes of GC patients. Moreover, the effect of biomarkers in exosomes on migration of GC cells was analyzed by transwell assay. RESULTS: Ten candidate biomarkers (AGT, SERPINH1, WNT2, LIPG, PLAU, COL1A1, MMP7, MXRA5, CXCL1 and COL11A1) were identified with efficient diagnostic value in GC. A prognostic gene signature consisted of AGT, SERPINH1 and MMP7 was constructed and showed a good performance in predicting overall survivals in TCGA. Consistently, serum levels of the three biomarkers also showed high sensitivity and specificity in distinguishing GC patients from controls. In addition, the expression level of the three biomarkers were associated with malignant degree and decreased after surgery in GC patients. Moreover, the expression level of AGT and MMP7 in exosomes correlated positively with serum level. The exosomes derived from serum of GC patients can promote migration of SGC-7901 cells. After neutralized the expression level of three proteins in exosomes with antibodies, the migration of GC cells was obviously suppressed. CONCLUSIONS: Our findings provided a novel strategy to identify diagnostic biomarkers based on public datasets, and suggested that the three-gene signature was a candidate diagnostic and prognostic biomarker for patients with GC.

480-nm distributed-feedback InGaN laser diode for 10.5-Gbit/s visible-light communication.

In this Letter, we demonstrate a novel distributed-feedback (DFB) InGaN-based laser diode with narrow-linewidth emission at ∼480nm (sky blue) and its application to high-speed visible-light communication (VLC). A significant side-mode suppression ratio (SMSR) of 42.4 dB, an optical power of ∼14mW, and a resolution-limited linewidth of ∼34pm were obtained under continuous-wave operation. A 5-Gbit/s VLC link was realized using non-return-to-zero on-off keying modulation, whereas a high-speed 10.5-Gbit/s VLC data rate was achieved by using a spectral-efficient 16-quadrature-amplitude-modulation orthogonal frequency-division multiplexing scheme. The reported high-performance sky-blue DFB laser is promising in enabling unexplored dense wavelength-division multiplexing schemes in VLC, narrow-line filtered systems, and other applications where single-frequency lasers are essential such as atomic clocks, high-resolution sensors, and spectroscopy. Single-frequency emitters at the sky-blue wavelength range will further benefit applications in the low-path-loss window of underwater media as well as those operating at the H-beta Fraunhofer line at ∼486nm.

A PPh3-catalyzed sequential annulation reaction to construct cyclopentane-fused dihydropyrazolone-pyrrolidinediones.

A PPh3-catalyzed sequential cycloaddition of maleimides with unsaturated pyrazolones has been developed. This protocol provides a simple and practical strategy for the construction of dispirocyclopentyl-[dihydropyrazolone-pyrrolidinedione] pyrrolidinedione skeletons containing five contiguous stereogenic centers, including two spiro-quaternary centers, with moderate yields (34-73%) and excellent diastereoselectivities (>20 : 1).

Promotion of esophageal adenocarcinoma metastasis via Wnt/ß-catenin signal pathway by sorting nexins 3.

BACKGROUND: Esophageal adenocarcinoma is often associated with late diagnoses, poor prognoses, significant morbidities, and high mortality rates. Aberrant expression of Wnt/ß-catenin signal pathways were observed in the tumorigenesis and metastasis of esophageal adenocarcinoma. Sorting nexins 3 has been shown to participate in Wnt protein sorting and regulate Wnt/ß-catenin signal transduction. Thus, we studied the role and molecular mechanism of sorting nexins 3 in esophageal adenocarcinoma. METHODS: Tissue microassay were used to analyze the expression of sorting nexins 3 in esophageal adenocarcinoma tissue and its relationship with survival rate. Using in vivo and in vitro models, we further investigated the effect of sorting nexins 3 on tumor growth and metastasis and underling mechanism. RESULTS: Immunohistochemical staining of human esophageal adenocarcinoma tissue microassay revealed an increased sorting nexins 3 level in esophageal adenocarcinoma tissue and high expression of sorting nexins 3 correlated with the poor prognosis. In vitro study showed that sorting nexins 3 knockdown suppressed esophageal adenocarcinoma cell invasion, metastasis, and epithelial-mesenchymal translation (EMT) process, and this result was confirmed by in vivo tumor metastasis assays. Moreover, we further proved that sorting nexins 3 affected cell invasion and EMT through Wnt/ß-catenin signal pathway. CONCLUSION: Our data provided strong evidence that sorting nexins 3 played a critical role in esophageal adenocarcinoma metastasis through Wnt/ß-catenin signal pathway.

On the realization of across wavy water-air-interface diffuse-line-of-sight communication based on an ultraviolet emitter.

We experimentally demonstrated high-speed diffuse line-of-sight optical wireless communication across a wavy water-air-interface. The testbed channel was evaluated, in terms of data rate, coverage and robustness to the dynamic wave movement, based on the performance of different modulation schemes, including non-return-to-zero on-off keying (NRZ-OOK) and quadrature amplitude modulation (QAM)-orthogonal frequency division multiplexing (OFDM). Under the emulated calm water condition, 8-QAM-OFDM offers a data rate of 111.4 Mbit/s at the aligned position, while only 55 Mbit/s is achieved using NRZ-OOK. On the other hand, effective communication can still be maintained at a high data rate of 11 Mbit/s when the photodetector is off aligned laterally by 5 cm based on NRZ-OOK modulation, leading to a coverage of ~79 cm2. By utilizing OFDM modulation scheme, a data rate of 30 Mbit/s can be achieved up to 2.5-cm misalignment, leading to a coverage of ~20 cm2. Furthermore, in the presence of strong waves (15-mm wave height, causing a scintillation index of 0.667), 4-QAM-OFDM modulation showed a better resilience to channel instability than NRZ-OOK modulation. Our studies pave the way for the eventual realization of communication across a challenging water-air interface without the need for an interface relay, which is much sought-after for implementing a robust and large-coverage underwater-to-terrestrial internet-of-things.

Toward self-powered and reliable visible light communication using amorphous silicon thin-film solar cells.

Enhancing robustness and energy efficiency is critical in visible light communication (VLC) to support large-scale data traffic and connectivity of smart devices in the era of fifth-generation networks. To this end, we demonstrate that amorphous silicon (a-Si) thin-film solar cells with a high light absorption coefficient are particularly useful for simultaneous robust signal detection and efficient energy harvesting under the condition of weak light in this study. Moreover, a first-generation prototype called AquaE-lite is developed that consists of an a-Si thin-film solar panel and receiver circuits, which can detect weak light as low as 1 µW/cm2. Using AquaE-lite and a white-light laser, orthogonal frequency-division multiplexing signals with data rates of 1 Mb/s and 908.2 kb/s are achieved over a 20-m long-distance air channel and 2.4-m turbid outdoor pool water, respectively, under the condition of strong background light. The reliable VLC system based on energy-efficient a-Si thin-film solar cells opens a new pathway for future satellite-air-ground-ocean optical wireless communication to realize connectivity among millions of Internet of Things devices.