Inhibition of SET domain-containing (lysine methyltransferase) 7 alleviates cognitive impairment through suppressing the activation of NOD-like receptor protein 3 inflammasome in isoflurane-induced aged mice.

BACKGROUND: As a common postoperative complication to elderly patients, postoperative cognitive dysfunction (POCD) is a central nervous system complication, often taking place after anesthesia and surgery. (Su(var)3-9, enhancer-of-zeste, and trithorax) domain-containing protein 7 (SETD7) plays important roles in metabolic-related diseases, viral infections, tumor formation, and some inflammatory reactions. However, the role and mechanism of SETD7 in POCD have not been previously studied. METHODS: RT-PCR and Western blot were performed to evaluate the efficiency of knockdown of SETD7. The pathological changes of hippocampal neurons in isoflurane-anesthetized mice were detected by HE staining, and the Morris water maze experiment was performed to evaluate the learning and memory abilities of mice. The effect of SETD7 on the hippocampus in isoflurane-induced aged mice was examined by Western blot and TUNEL assay. Then ELISA assay was applied to determine the expression of some inflammatory cytokines, followed by the detection of expression of NOD-like receptor protein 3 (NLRP3) inflammasome through Western blot. RESULTS: The data of this research revealed that SETD7 knockdown improved cognitive impairment in isoflurane-anesthetized mice, ameliorated cell pyroptosis, inhibited the release of inflammatory cytokines, and suppressed the activation of NLRP3 inflammasome in the hippocampus in isoflurane-induced aged mice. CONCLUSION: Collectively, these results provided evidence that the inhibition of SETD7 could alleviate neuroinflammation, pyroptosis, and cognitive impairment by suppressing the activation of the NLRP3 inflammasome in isoflurane-induced aged mice.

Diagnostic value of endoscopic ultrasound for detecting pancreatic neuroendocrine tumors: A systematic review and meta-analysis.

BACKGROUND: Endoscopic ultrasound (EUS) is widely used as a cost-effective method for detecting pancreatic neuroendocrine tumors (PNTs), but its diagnostic value is variable among published studies. This meta-analysis aimed to determine the diagnostic value of EUS for PNTs. METHODS: Three electronic databases, including PubMed, Embase, and the Cochrane Library, were searched for studies published up to July 2018. The summary sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and receiver operating characteristic (ROC) curve were calculated to evaluate the diagnostic value of EUS using the random-effects model. RESULTS: Thirteen studies involving 609 patients were included in this meta-analysis. The summary sensitivity and specificity of EUS for detecting PNTs were 0.86 and 0.89, respectively. The PLR and NLR of EUS were 7.81 and 0.15, respectively. The DOR of EUS for diagnosing PNTs was 24.20. The area under the ROC was 0.90. Finally, the subgroup analyses indicated that publication year and percentage of males could introduce potential biases for the DOR of EUS. CONCLUSIONS: This meta-analysis suggests that EUS has a relatively high diagnostic value for diagnosing PNTs.

circPUM1 Activates the PI3K/AKT Signaling Pathway by Sponging to Promote the Proliferation, Invasion and Glycolysis of Pancreatic Cancer.

BACKGROUND: Our study seeks to obtain data to assess the impact of circPUM1 on pancreatic cancer (PC) and its mechanism. METHODS: The expression of circPUM1 and miR-200c-3p in PC and normal tissues and PC cell lines was collected and detected, and subsequently dual-luciferase assay-based verification of the binding site of the two was carried out. After interfering with circPUM1 expression in MIAPaCa-2 and PANC-1 cells, cell proliferation, viability, apoptosis rate, invasion ability, glucose consumption, and lactate production were measured by MTT, colony formation, flow cytometry, Transwell assays, and glucose and lactate assay kits. Additionally, western blot was utilized for assessing PI3K/AKT signaling pathway-related proteins. From the results, highly expressed circPUM1 and miR-200c-3p in PC tissues and cells were proved. RESULTS: Down-regulation of circPUM1 expression significantly inhibited cell proliferation, cell viability, invasion and glycolysis, while increasing the apoptosis rate. Down-regulated circPUM1 led to the inhibition of the PI3K/AKT signaling pathway activity in PC cells; while up-regulated circPUM1 increased its activity. Further experiments revealed that down-regulation of miR-200c-3p expression reversed the inhibitory effect of lowly expressed circPUM1 on PC cells. CONCLUSION: In summary, circPUM1 activates PI3K/AKT signaling pathway by sponging miR-200c-3p and promotes PC progression.

Tumor burden score dictates prognosis of patients with combined hepatocellular cholangiocarcinoma undergoing hepatectomy.

Background: The prognostic value of the tumor burden score (TBS) in patients with combined hepatocellular-cholangiocarcinoma (cHCC-CCA) remains unknown. This study aimed to investigate the impact of TBS on long-term outcomes after surgery. Methods: Patients who underwent radical-intent resection between June 2013 and December 2019 were retrospectively reviewed. Kaplan-Meier curves were used to analyze patient survival, and disease-free survival (DFS) and overall survival (OS) were examined in relation to TBS. Results: A total of 178 patients were included in this study, with 119 in the training cohort and 59 in the validation cohort. Kaplan-Meier curves showed that TBS was a strong prognostic indicator in patients with cHCC-CCA. Elevated TBS was associated with poorer DFS and OS (both P-value < 0.001) and was identified as an independent prognostic indicator. In addition, the prognostic value of TBS outperformed tumor size and number alone, microvascular invasion, and lymph node invasion. The prognostic significance of TBS was confirmed by the internal validation cohort. Conclusions: The present study suggested the significance of tumor morphology in assessing the prognosis of patients with cHCC-CCA who undergoing curative resection. The TBS is a promising prognostic index in patients with cHCC-CCA. Elevated TBS was related to a lower long-term survival rate and was identified as an independent risk factor for poor DFS and OS. Further research is needed to verify our results.

Hybrid integrated InP-Si3N4 diode laser with a 40-Hz intrinsic linewidth.

We demonstrate a hybrid integrated and widely tunable diode laser with an intrinsic linewidth as narrow as 40 Hz, achieved with a single roundtrip through a low-loss feedback circuit that extends the cavity length to 0.5 meter on a chip. Employing solely dielectrics for single-roundtrip, single-mode resolved feedback filtering enables linewidth narrowing with increasing laser power, without limitations through nonlinear loss. We achieve single-frequency oscillation with up to 23 mW fiber coupled output power, 70-nm wide spectral coverage in the 1.55 µm wavelength range with 3 mW output and obtain more than 60 dB side mode suppression. Such properties and options for further linewidth narrowing render the approach of high interest for direct integration in photonic circuits serving microwave photonics, coherent communications, sensing and metrology with highest resolution.

Ring resonator enhanced mode-hop-free wavelength tuning of an integrated extended-cavity laser.

Extending the cavity length of diode lasers with feedback from Bragg structures and ring resonators is highly effective for obtaining ultra-narrow laser linewidths. However, cavity length extension also decreases the free-spectral range of the cavity. This reduces the wavelength range of continuous laser tuning that can be achieved with a given phase shift of an intracavity phase tuning element. We present a method that increases the range of continuous tuning to that of a short equivalent laser cavity, while maintaining the ultra-narrow linewidth of a long cavity. Using a single-frequency hybrid integrated InP-Si3N4 diode laser with 120 nm coverage around 1540 nm, with a maximum output of 24 mW and lowest intrinsic linewidth of 2.2 kHz, we demonstrate a six-fold increased continuous and mode-hop-free tuning range of 0.22 nm (28 GHz) as compared to the free-spectral range of the laser cavity.

Long non-coding RNA TGLC15 advances hepatocellular carcinoma by stabilizing Sox4.

BACKGROUND: The hepatocellular carcinoma (HCC) belongs to a common malignancy especially in China. Recent data have clarified important roles of long non-coding RNAs (lncRNAs) in HCC. However, the role of a novel intergenic lncRNA termed TGLC15 is still elusive. METHODS: We screened for novel lncRNAs using lncRNA profiling. TGLC15 expression was quantified by qRT-PCR. In vitro experiments such as migration and viability assays were performed. In vivo implantation experiments were conducted to investigate tumorigenic functions of TGLC15. Combined RNA immunoprecipitation (RIP) and mass spectrometry (MS) were utilized to uncover Sox4 as TGLC15 binding protein. RESULTS: TGLC15 is significantly overexpressed in tumor tissues and HCC cell lines. Higher TGLC15 levels correlated with advanced malignant characteristics such as TNM stages, tumor size, and metastasis. TGLC15 advanced HCC migration and viability. The in vivo experiments supported that xenograft tumor growth and proliferation were facilitated by TGLC15 overexpression. Mechanistic studies showed that TGLC15 interacted with Sox4 and interaction between TGLC15 and Sox4 could stabilize Sox4 via reduction in proteasome-mediated degradation. CONCLUSIONS: Collectively, our data have identified a novel lncRNA TGLC15 during HCC development. The TGLC15-Sox4 signaling might be a potential target for pharmaceutical intervention.

HIF-1-miR-219-SMC4 Regulatory Pathway Promoting Proliferation and Migration of HCC under Hypoxic Condition.

This paper aims to investigate the function of structural maintenance of chromosome 4 (SMC4) in the progression of hepatocellular carcinoma (HCC) under hypoxic condition. In this study, we found that suppression of SMC4 could inhibit proliferation and migration of HCC cells through inducing G1 phase arrest and affecting process of epithelial-mesenchymal transition (EMT) under hypoxic condition. Moreover, we demonstrated that SMC4 was transcriptionally regulated by hypoxia-inducible factor-1 (HIF-1) under hypoxic condition. As SMC has been shown to be a target gene of miR-219, we observed that miR-219 was downregulated under hypoxic condition and suppression of HIF-1a could lead to the upregulation of miR-219. We also proved that miR-219 could affect the proliferation and migration of HCC cells under hypoxic condition. In conclusion, our study demonstrated a novel HIF-1-miR-219-SMC4 regulatory pathway under hypoxic condition in HCC cells.

Linewidth narrowing via low-loss dielectric waveguide feedback circuits in hybrid integrated frequency comb lasers.

We present an integrated hybrid semiconductor-dielectric (InP-Si3N4) waveguide laser that generates frequency combs at a wavelength around 1.5 µm with a record-low intrinsic optical linewidth of 34 kHz. This is achieved by extending the cavity photon lifetime using a low-loss dielectric waveguide circuit. In our experimental demonstration, the on-chip, effective optical path length of the laser cavity is extended to 6 cm. The resulting linewidth narrowing shows the high potential of on-chip, highly coherent frequency combs with direct electrical pumping, based on hybrid and heterogeneous integrated circuits making use of low-loss dielectric waveguides.

Clinicopathological and prognostic significance of platelet-to-lymphocyte ratio in patients with hepatocellular carcinoma.

The platelet-to-lymphocyte ratio (PLR) is reported to be a prognostic factor in multiple malignancies. The aim of this study was to assess its prognostic value in hepatocellular carcinoma (HCC). We performed comprehensive searches of electronic databases for relevant studies. A total of eleven studies comprising 2,507 patients were included. Elevated PLR was significantly associated with poor overall survival (OS) (HR = 1.78; 95% CI = 1.36-2.34; P < 0.001) and disease-free survival (DFS)/recurrence-free survival (RFS) (HR = 1.82; 95% CI = 1.56-2.13; P < 0.001). The findings from most subgroup analyses were consistent with those from the overall analysis. In addition, a high PLR correlated with tumor size > 3 cm, TNM stage, lymph node metastasis, distant metastasis, and vascular invasion. We therefore conclude that elevated pretreatment PLR may be predicative of a poor prognosis in patients with HCC.