Broadband Room-Temperature Photodetection via InBiTe3 Nanosheet.

Broadband room-temperature photodetection has become a pressing need as application requirements for communication, imaging, spectroscopy, and sensing have evolved. Topological insulators (TIs) have narrow bandgap structures with a wide absorption spectral response range, which should meet the requirements of broadband detection. However, owing to their high carrier concentration and low carrier mobility resulting in poor noise equivalent power (NEP), they are generally considered unsuitable for photodetection. Here, InBiTe3 alloy nanosheet formed by doping In2Te3 into Bi2Te3(≈ 1:1) is utilized, effectively improving carrier mobility by over ten times while maintaining a narrow bandgap structure, to fabricate a broadband photodetector covering a wide response range from visible to millimeter wave (MMW). Under the synergistic multi-mechanism of the photoelectric effect in the visible-infrared region and the electromagnetic-induced potential well (EIW) effect in Terahertz band, the performance of NEP = 75 pW Hz-1/2 and response time τ ≈100 µs in visible to infrared band and the performance of NEP = 6.7 × 10-3 pW Hz-1/2, τ ≈8 µs in Terahertz region are achieved. The results demonstrate the promising prospects of topological insulator alloy (like InBiTe3) nanosheet in optoelectronic detection applications and provide a direction for the research into high-performance broadband photoelectric detectors via TIs.

Effect of Premedication With Pronase Before Upper Gastrointestinal Endoscopy: A Multicenter Prospective Randomized Controlled Study.

OBJECTIVES: This study aimed to confirm whether premedication with pronase before endoscopy improves mucosal visualization and increases precancerous lesion and cancer lesion detection rates. MATERIALS AND METHODS: From June 2018 to April 2019, out-patients scheduled for endoscopy from 13 hospitals were screened to be randomly allocated in a 2:1 ratio to premedication with pronase (group A) and water (group B). The primary endpoint was mucosal visibility scores, and the secondary endpoint was precancerous and cancer lesion detection rates. This trial was registered at Chinese Clinical Trial Registry, and the registration number was ChiCTR1800016853. RESULTS: Group A showed significantly lower mucosal visibility scores (better mucosal visibility) of esophagus, stomach, and duodenum than group B, with all P -values <0.001. The overall cancer detection rates between group A and group B were 0.83 and 1.08%, and overall detection rates of precancerous and cancer lesion were 4.4 and 4.9%, both without significant difference ( P =1.000 and 0.824). In addition, the flushing volume (milliliter) of group A (10.52±23.41) was less than group B (36.30±52.11) ( P <0.001), and the flushing frequency of group A (0.46±1.01) was fewer than group B (1.62±2.12) ( P <0.001). CONCLUSIONS: Premedication with pronase could achieve better mucosal visibility and decrease flushing frequency and volume, but may not increase lesion detection rates.

Comprehensive analysis of single-cell RNA-seq and bulk RNA-seq revealed the heterogeneity and convergence of the immune microenvironment in renal cell carcinoma.

Substantial progress has been made in cancer biology and treatment in recent years, but the clinical outcome of patients with renal cell carcinoma (RCC) remains unsatisfactory. The tumor microenvironment (TME) is a potential target. By analyzing single-cell RNA sequencing (sc-RNAseq) data from six RCC tumor samples, this study identified 11 different cell types in the RCC cellular microenvironment, indicating a high degree of intratumoral heterogeneity. Through re-dimensionality reduction clustering of epithelial cells, neutrophils, macrophages, and T cells, we deeply reveal differences in the RCC tumor microenvironment. By analyzing differentially expressed genes in normal epithelial cells and malignant epithelial cells, we identify RNASET2 and GATM as potential prognostic biomarkers in RCC. In addition, by transcriptional factor analysis, we found significant differences in the expression of GZMK-CD8 T cell and B cell transcription factors between cancer tissues and normal tissues. By cell correlation analysis, we found significant correlations between neutrophils and macrophages and between IL7R-CD4 T cells and T regulatory (Treg) cells in RCC, which may be involved in the formation of immune TMEs. By cell developmental trajectory analysis, we showed that macrophages may be derived from neutrophils, whereas Treg cells may be derived from IL7R-CD4 T cells. By cell communication analysis, we found a clear interaction between macrophages and endothelial cells, neutrophils, and GZMK-CD8 T cells. In addition, we found that ADGRE5 signaling was mainly derived from mast cells and GZMK-CD8 T cells, and had a significant communication effect with neutrophils. The COLLAGEN signaling pathway is mainly derived from fibroblasts and has a significant communication effect with mast cells. Finally, we verified that RNASET2, which is highly expressed in epithelial cells, promotes proliferation and migration of RCC in vitro. RNASET2 is likely to be a potential target for renal cell carcinoma therapy. The results based on sc-RNAseq data analysis help to further elucidate the cellular microenvironment of RCC and provide help for cancer heterogeneity studies. This will help to provide more accurate personalized treatment for patients in clinical diagnosis.

Research on Similarity Simulation Experiment of Mine Pressure Appearance in Surface Gully Working Face Based on BOTDA.

In order to study the mountain deflection characteristics and the pressure law of the working face after the mining of a shallow coal seam under the valley terrain, a geometric size of 5.0 × 0.2 × 1.33 m is used in the physical similarity model. Brillouin optical time domain analysis (BOTDA) technology is applied to a similar physical model experiment to monitor the internal strain of the overlying rock. In this paper, the strain law of the horizontal optical fiber at different stages of the instability of the mountain structure is analyzed. Combined with the measurement of the strain field on the surface of the model via digital image correlation (DIC) technology, the optical fiber strain characteristics of the precursor of mountain instability are given. The optical fiber characterization method of working face pressure is proposed, and the working face pressures at different mining stages in gully terrain are characterized. Finally, the relationship between the deflection instability of the mountain and the strong ground pressure on the working face is discussed. The sudden increase in the strain peak point of the horizontally distributed optical fiber strain curve can be used to distinguish the strong ground pressure. At the same time, this conclusion is verified by comparing the measured underground ground pressure values. The research results can promote the application of optical fiber sensing technology in the field of mine engineering.

Tunable and coherent terahertz source based on CdSiP2 crystal via collinear difference frequency generation.

CdSiP2 (CSP) crystals have attracted increasing attention as efficient optical conversion media. Herein, the optical properties of a CSP crystal grown with the vertical Bridgman method are measured by a terahertz time-domain spectrometer (THz-TDS) at 0.2-3 THz. For the first time, to the best of our knowledge, the broadband, tunable, coherent, monochromatic THz radiation from 0.08 to 1.68 THz (3775-178 µm) is generated experimentally via this crystal, which is pumped by a nanosecond Q-switched Nd:YAG laser and an optical parametric oscillator (OPO) and based on difference frequency generation (DFG) technology. The output power and its corresponding conversion efficiency at 0.74 THz are 26.6 mW and 1.4 × 10-7, respectively. Our work demonstrates that the CSP crystal is a potential efficient terahertz DFG candidate for out-of-door applications.

Hyperlipemia pancreatitis onset time affects the association between elevated serum triglyceride levels and disease severity.

BACKGROUND: The association of serum triglyceride (TG) levels with the severity of hypertriglyceridaemia-induced acute pancreatitis (HTG-AP) remains controversial. This study aimed to comprehensively assess the TG levels from the initial onset and their predictive value in the disease assessment of HTG-AP. METHODS: Data collected from January 2018 to July 2021 in one institute were assessed retrospectively. HTG-AP was defined as a TG level > 500 mg/dL in the absence of other common aetiologies of AP. The TG levels within 24 hours (24 h), 48 hours (48 h), 3-4 days (3-4 d), and 5-7 days (5-7 d) after symptom onset and their correlations with disease severity in HTG-AP patients were analysed by cross-sectional and longitudinal studies. RESULTS: In the cross-sectional study, 377 HTG-AP patients were included before lipid-lowering intervention: 216 subjects had their first TG levels measured within 24 h after onset, 91 within 48 h, 50 in 3-4 d, and 20 in 5-7 d. TG levels decreased in the 24 h, 48 h and 3-4 d groups (P < 0.001), however, the TG decline in the 5-7 d group had no difference compared with the 3-4 d group. HTG-AP patients with severe or moderately severe disease displayed higher TG levels than those with mild disease in the 24 h and 48 h groups (P < 0.050) but not in the 3-4 d or 5-7 d groups. Furthermore, the TG levels were correlated with the modified computed tomography severity index only in the 24 h and 48 h groups, while an association between serum calcium levels and C-reactive protein levels was only present in the 24 h group. Similarly, the TG levels were related to hospital days and ICU days in the 24 h and/or 48 h groups. In the longitudinal study, 165 patients with complete records of TG levels from 24 h to 5-7 d were enrolled. With supportive care and lipid-lowering treatment after admission, the TG levels declined rapidly (P < 0.001), and the correlations with disease severity weakened or even disappeared from 24 h to 5-7 d. CONCLUSION: TG levels decreased and attenuated the association with disease severity of HTG-AP over the time of onset. The TG levels within the initial 48 h after onset were most useful for the diagnosis and disease assessment of HTG-AP.

CT, MRI, and 18F-FDG PET/CT imaging features of seven cases of adult pancreatoblastoma.

OBJECTIVE: This study mainly analysed the imaging data for seven cases of adult pancreatoblastoma (PB) and summarized additional imaging features of this disease based on a literature review, aiming to improve the understanding and diagnosis rate of this disease. MATERIALS AND METHODS: The imaging data for seven adult patients pathologically diagnosed with adult PB were retrospectively analysed. Among the seven patients, six underwent computed tomography (CT) scans, two patients underwent abdominal magnetic resonance imaging (MRI), and five patients underwent 18F-FDG PET/CT. RESULTS: The tumours were located in the head of the pancreas in three cases, in the tail of the pancreas in two cases, and in the gastric antrum and neck of the pancreas in one case. Six tumours showed blurred edges, and an incomplete envelope was observed in only two cases when enhanced, which showed extruded growth and cyst-solid masses; one tumour was a solid mass with ossification. Showing mild or significant enhancement in the arterial phase (AP) for six cases. In the MRI sequence, isointensity was found on suppressed T1-weighted imaging, and hyperintensity was noted on suppressed T2-weighted imaging in two cases, with significant enhancement. Pancreatic duct dilatation was found in four cases. Tumour 18F-FDG PET/CT imaging exhibited high uptake in five cases. CONCLUSION: Adult PB involves a single tumour and commonly manifests as cystic-solid masses with blurred edges. Capsules are rare, ossification is an important feature, tumours can also present in ectopic pancreatic tissues, with mild or strengthening in the AP, and 18F-FDG uptake is high. These features are relatively specific characteristics in adult PB.

Single-cell RNA sequencing of psoriatic skin identifies pathogenic Tc17 cell subsets and reveals distinctions between CD8+ T cells in autoimmunity and cancer.

BACKGROUND: Psoriasis is an inflammatory, IL-17-driven skin disease in which autoantigen-induced CD8+ T cells have been identified as pathogenic drivers. OBJECTIVE: Our study focused on comprehensively characterizing the phenotypic variation of CD8+ T cells in psoriatic lesions. METHODS: We used single-cell RNA sequencing to compare CD8+ T-cell transcriptomic heterogeneity between psoriatic and healthy skin. RESULTS: We identified 11 transcriptionally diverse CD8+ T-cell subsets in psoriatic and healthy skin. Among several inflammatory subsets enriched in psoriatic skin, we observed 2 Tc17 cell subsets that were metabolically divergent, were developmentally related, and expressed CXCL13, which we found to be a biomarker of psoriasis severity and which achieved comparable or greater accuracy than IL17A in a support vector machine classifier of psoriasis and healthy transcriptomes. Despite high coinhibitory receptor expression in the Tc17 cell clusters, a comparison of these cells with melanoma-infiltrating CD8+ T cells revealed upregulated cytokine, cytolytic, and metabolic transcriptional activity in the psoriatic cells that differed from an exhaustion program. CONCLUSION: Using high-resolution single-cell profiling in tissue, we have uncovered the diverse landscape of CD8+ T cells in psoriatic and healthy skin, including 2 nonexhausted Tc17 cell subsets associated with disease severity.

ß-Catenin Is Required for the cGAS/STING Signaling Pathway but Antagonized by the Herpes Simplex Virus 1 US3 Protein.

The cGAS/STING-mediated DNA-sensing signaling pathway is crucial for interferon (IFN) production and host antiviral responses. Herpes simplex virus I (HSV-1) is a DNA virus that has evolved multiple strategies to evade host immune responses. Here, we demonstrate that the highly conserved ß-catenin protein in the Wnt signaling pathway is an important factor to enhance the transcription of type I interferon (IFN-I) in the cGAS/STING signaling pathway, and the production of IFN-I mediated by ß-catenin was antagonized by HSV-1 US3 protein via its kinase activity. Infection by US3-deficienct HSV-1 and its kinase-dead variants failed to downregulate IFN-I and IFN-stimulated gene (ISG) production induced by ß-catenin. Consistent with this, absence of ß-catenin enhanced the replication of US3-deficienct HSV-1, but not wild-type HSV-1. The underlying mechanism was the interaction of US3 with ß-catenin and its hyperphosphorylation of ß-catenin at Thr556 to block its nuclear translocation. For the first time, HSV-1 US3 has been shown to inhibit IFN-I production through hyperphosphorylation of ß-catenin and to subvert host antiviral innate immunity.IMPORTANCE Although increasing evidence has demonstrated that HSV-1 subverts host immune responses and establishes lifelong latent infection, the molecular mechanisms by which HSV-1 interrupts antiviral innate immunity, especially the cGAS/STING-mediated cellular DNA-sensing signaling pathway, have not been fully explored. Here, we show that ß-catenin promotes cGAS/STING-mediated activation of the IFN pathway, which is important for cellular innate immune responses and intrinsic resistance to DNA virus infection. The protein kinase US3 antagonizes the production of IFN by targeting ß-catenin via its kinase activity. The findings in this study reveal a novel mechanism for HSV-1 to evade host antiviral immunity and add new knowledge to help in understanding the interaction between the host and HSV-1 infection.

Predictive value of fibrinogen in identifying inflammatory bowel disease in active stage.

BACKGROUND: We aimed to externally validate for the first time the diagnostic ability of fibrinogen to identify active inflammatory bowel disease (IBD). METHODS: The research totally involved 788 patients with IBD, consisted of 245 ulcerative colitis (UC) and 543 Crohn' s disease (CD). The Mayo score and Crohn disease activity index (CDAI) assessed disease activity of UC and CD respectively. The independent association between fibrinogen and disease activity of patients with UC or CD was investigated by multivariate logistic regression analyses. Area under the receiver operating characteristic curve (AUROC) assessed the performance of various biomarkers in discriminating disease states. RESULTS: The fibrinogen levels in active patients with IBD significantly increased compared with those in remission stage (P < 0.001). Fibrinogen was an independent predictor to distinguish disease activity of UC (odds ratio: 2.247, 95% confidence interval: 1.428-3.537, P < 0.001) and CD (odds ratio: 2.124, 95% confidence interval: 1.433-3.148, P < 0.001). Fibrinogen was positively correlated with the Mayo score (r = 0.529, P < 0.001) and CDAI (r = 0.625, P < 0.001). Fibrinogen had a high discriminative capacity for both active UC (AUROC: 0.806, 95% confidence interval: 0.751-0.861) and CD (AUROC: 0.869, 95% confidence interval: 0.839-0.899). The optimum cut-off values of fibrinogen 3.22 was 70% sensitive and 77% specific for active UC, and 3.87 was 77% sensitive and 81% specific for active CD respectively. CONCLUSIONS: Fibrinogen is a convenient and practical biomarker to identify active IBD.

Premedication with reformulated simethicone and sodium bicarbonate improves mucosal visibility during upper gastrointestinal endoscopy: a double-blind, multicenter, randomized controlled trial.

BACKGROUND: The reformulated simethicone emulsion from Berlin Chemical AG might develop white flocculate precipitate covering the gastric mucosa when used before esophagogastroduodenoscopy (EGD). We aim to investigate whether combining the reformulated simethicone emulsion with 5% sodium bicarbonate solution could prevent the development of white precipitate and improve visibility during EGD. METHODS: Our clinical study involved 523 patients. They were randomly assigned to two groups. In Group A, patients received a warm solution containing 30 ml 5% sodium bicarbonate solution and 15 ml reformulated simethicone emulsion. In Group B, patients received 45 ml 40 °C lukewarm water. Visibility scores were recorded and analyzed. Flushes, volume of flush water, overall time taken for EGD and complications during or after the procedure were also recorded. RESULTS: We found that no white precipitate was observed during EGD in Group A. Moreover, visibility scores in Group A were significantly lower (P < 0.01). Patients in Group A had fewer flushes (P < 0.01) and smaller volume of flush water (P < 0.01). In addition, the overall time taken for the EGD procedure was significantly shorter in Group A (P < 0.01). The percentage of patients who had no adverse response was significantly higher in Group A than in Group B (P < 0.01). CONCLUSIONS: Premedication with a mixed solution of 15 ml reformulated simethicone emulsion and 30 ml 5% sodium bicarbonate solution can prevent the development of white precipitate, substantially enhancing mucosal visibility safely. TRIAL REGISTRATION: The registered name of the trial is "Efficacy of using premedication with reformulated simethicone emulsion during upper gastrointestinal endoscopy examination". Its Current Controlled Trials number is ChiCTR1900021689. Its date of registration is 11 September 2019. Retrospectively registered, http://www.medresman.org.cn/uc/sindex.aspx .

Contact tracing of syphilis-seropositive pregnant women and syphilis-infection among their male partners in Bao'an district, Shenzhen, China.

BACKGROUND: Untreated male partners are a critical source of maternal re-infection. Contact tracing is a good way to identify infection among partners and reduce risk of mother-to-child transmission related to maternal re-infection. This study aimed to analyze the current situation and related factors of contact tracing of syphilis-seropositive pregnant women and syphilis-infection among their male partners. METHOD: Data of syphilis-seropositive pregnant women and their male partners attending clinic for syphilis-screening were obtained from the Shenzhen Program for Prevention of Congenital Syphilis. Contact tracing rate of syphilis-seropositive pregnant women and syphilis prevalence among male partners were counted, and related factors were also analyzed using a random-effects logistic regression model. RESULT: Of the 1299 syphilis-seropositive pregnant women, 74.1% (963/1299) had their male partners receiving syphilis-screening and 19.1% (184/963) of male partners were syphilis-infected. For pregnant women, being divorced (adjusted odds ratio [AOR] =0.39; 95%CI: 0.17-0.87), seeking for emergency services at their first antenatal clinics visits (AOR = 0.58; 95%CI: 0.44-0.77), reporting willingness to notify partner(AOR = 7.65; 95%CI: 4.69-12.49), multi-partners (AOR = 1.38; 95%CI:1.03-1.86) and having a history of drug abuse (AOR = 0.37; 95%CI: 0.14-1.00)were independently associated with successful contact tracing. For male partners, of minority ethnicity (AOR = 4.15; 95%CI: 1.66-10.34), age at first sex>20(AOR = 0.57; 95%CI: 0.37-0.87), reporting multi-partners (AOR = 1.60; 95%CI: 1.04-2.46), having a history of drug abuse (AOR = 4.07; 95%CI: 1.31-12.64) were independently associated with syphilis-infection. In addition, pregnant women with TRUST titer ≥1:8 (AOR = 2.81; 95%CI: 1.87-4.21), having a history of adverse pregnancy outcomes (AOR = 1.70; 95%CI: 1.14-2.53), reporting multi-partners (AOR = 0.43; 95%CI: 0.29-0.64) and reporting the current partner as the source of syphilis (AOR = 5.05; 95%CI: 2.82-9.03) were independently associated with partners' syphilis-infection. CONCLUSION: Contact tracing is feasible and effective in identifying syphilis-infected partners among syphilis-seropositive pregnant women. Contact tracing is associated with many factors such as women's marital status, services at their first antenatal clinics visit and willingness of partner notification. Partners' ethnicity, age at first sex, multi-partners and history of drug abuse as well as women's levels of TRUST titer were associated with partners' syphilis-infection.

Data Mining the Prognostic Biomarkers: miRNAs Targeting the Chemotherapeutic Agent 5-Fluorouracil in Colon Cancer.

BACKGROUND: Colon cancer is one of the most common and has the highest mortality rate in the world. MicroRNAs (miRNAs) as potential biomarkers play crucial roles in diagnosis, prognosis, and drug-response prediction of colon cancer. METHODS: In this study, we collected miRNA expression data from the Broad GDAC Firehose and screened specific miRNA-gene pairs after treatment with 5-fluorouracil treatment and used COAD analysis to study the association of miRNAs and inhibitor of the inhibitory genes. Potential drug-related miRNAs were further extracted via hypergeometric testing. RESULTS: The results showed that 13,651 miRNA-gene pairs were retrieved, including 242 miRNAs and 5,179 genes. The association between miRNAs and the inhibitor of inhibitory genes DPYD, TYMS, UNG was indicated. We further extracted 4 potential drug-related miRNAs, including hsa-mir-551a, hsa-mir-144, hsa-mir-519b, hsa-mir-506. The miRNA-gene pairs associated with 5-fluorouracil exhibit better prognosis in patients with CRC. CONCLUSIONS: We expected that up-regulation of hsa-mir-551a, hsa-mir-144, and hsa-mir-506 and down-regulation of hsa-mir-519b would exhibit better prognosis. The findings would underpin the fundamental hypothesis of mi-RNAs being prognostic signal biomarkers in therapy of 5-fluorouracil in CRC.

Prognostic Value of Acute-On-Chronic Liver Failure (ACLF) Score in Critically Ill Patients with Cirrhosis and ACLF.

BACKGROUND In the intensive care unit (ICU), critically ill patients with cirrhosis and acute-on-chronic liver failure (ACLF) continue to have high mortality rates. The AARC ACLF score is a simple, newly-developed score based on Asian ACLF patients, which performs well in prognosis. The present study attempted to verify the prognostic ability of AARC ACLF in non-Asian critically ill patients with cirrhosis and ACLF. MATERIAL AND METHODS We enrolled 786 patients. Relevant clinical data were collected within 24 h after admission to compare the differences between survivors and non-survivors, and all the patients were followed up for at least 180 days. RESULTS The 28-day, 90-day, and 180-day mortality rates were 28.9% (227/786), 36.4% (286/786), and 40.3% (317/786), respectively. Multivariate Cox regression analysis showed that AARC ACLF score (HR: 1.375, 95% CI: 1.247-1.516, P<0.001) was an independent predictive factor of 28-day mortality, and the AUROC of the predictive ability in 28-day mortality of the AARC ACLF score was 0.754. In addition, the AARC ACLF score was regraded into 3 classes (low risk: AARC ACLF <9, intermediate risk: 9≤ AARC ACLF <12, and high risk: AARC ACLF ≥12). The AARC ACLF score can be used for dynamic assessment by retest at days 4-7. CONCLUSIONS The AARC ACLF score has a good predictive value for 28-day, 90-day, and 180-day mortality in non-Asian critically ill patients with cirrhosis and ACLF, which is not inferior to CLIF-C ACLFsLact and other models. It is easy to use at bedside, and it is dynamic and reliable.

Association between triglyceride glucose-body mass index and non-alcoholic fatty liver disease in the non-obese Chinese population with normal blood lipid levels: a secondary analysis based on a prospective cohort study.

BACKGROUND: Both triglyceride glucose-body mass index (TyG-BMI) and non-alcoholic fatty liver disease (NAFLD) are linked to insulin resistance (IR). Prospective studies linking TyG-BMI to NAFLD have been limited by short follow-up. This study investigated the longitudinal association between TyG-BMI and NAFLD occurrence in the non-obese Chinese individuals. METHODS: This study determined TyG-BMI at baseline and the incidence of NAFLD at follow-up and performed a post hoc analysis of a prospective cohort study that involved assessing the risk of NAFLD in non-obese Chinese residents from January 2010 to December 2014. The incidence of NAFLD during the 5-year follow-up was identified as the endpoint. Cox proportional hazards regression analysis was used to evaluate hazard ratios (HRs) and 95% confidence intervals (95% CIs) for the incidence of NAFLD. Receiver operating characteristic (ROC) curve analysis was conducted to estimate the predictive power of TyG-BMI and its components for NAFLD. Subgroup analysis was performed to better understand other factors that may affect the association between TyG-BMI and NAFLD to identify potential special populations. RESULTS: During the follow-up period, 841 (8.61%) of 9767 non-obese subjects who met the screening criteria were diagnosed with NAFLD. After confounding factors were fully adjusted for, the HR of NAFLD was 3.09 (95% CI 2.63-3.63) per standard deviation (SD) increase in TyG-BMI. Furthermore, TyG-BMI had a strong predictive value (area under ROC = 0.85; 95% CI 0.84-0.86) for the incidence of NAFLD, with a specificity of 0.73 and sensitivity of 0.82. Additionally, in the male population, each SD increase in TyG-BMI was linked to an increased risk of NAFLD (HR = 2.85, 95% CI 2.30-3.53), but the risk was higher in the female population (HR = 3.58, 95% CI 2.80-4.60). Gender and TyG-BMI interacted significantly with NAFLD incidence (P < 0.0001). CONCLUSION: In the normolipidaemic and non-obese subset of the Chinese population, an increase in TyG-BMI is related to an increased incidence of NAFLD. TyG-BMI may have clinical significance in identifying groups at high risk of NAFLD.

Influence of doping for InSb on ultrafast carrier dynamics measured by time-resolved terahertz spectroscopy.

The influence of doping on the ultrafast carrier dynamics in InSb has been studied by time-resolved terahertz spectroscopy with photogenerated carrier densities from 1.5×1018 to 9.5×1019cm-3 at 800 nm. The photoinduced absorption and carrier recovery process show doping type dependence. The carrier recovery time of intrinsic InSb is greater than that of p-doped InSb but less than that of n-doped InSb at low carrier densities. At high carrier densities, compared with intrinsic InSb, the doped InSb is more prone to transient Auger recombination, which indicates that the appearance of the fast decay process depends on the carrier densities. The photoinduced absorption of terahertz probe pulse of n-doped InSb is significantly less than that of p-doped and intrinsic InSb; however, that of p-doped InSb is close to that of intrinsic InSb, which demonstrates that the high concentration of electrons can accelerate the efficiency of transient Auger recombination. Our analysis provides assistance to the design, manufacture, and improvement of photovoltaic detectors.

Long noncoding RNA HOTTIP mediates SRF expression through sponging miR-150 in hepatic stellate cells.

HOXA transcript at the distal tip (HOTTIP) has been shown to be up-regulated in a variety of cancers and is identified as an oncogenic long noncoding RNA. However, the biological role of HOTTIP in liver fibrosis is unclear. Here, we reported that HOTTIP was specifically overexpressed in activated hepatic stellate cells (HSCs). HOTTIP knockdown suppressed the activation and proliferation of HSCs. Luciferase reporter assay showed that HOTTIP and serum response factor (SRF) were targets of miR-150. RNA binding protein immunoprecipitation assay indicated the interaction between miR-150 and HOTTIP. Further study revealed that HOTTIP increased SRF expression as a competing endogenous RNA for miR-150, thus prompting HSC activation. Taken together, we provide a novel HOTTIP-miR-150-SRF signalling cascade in liver fibrosis.

C/EBP homologous protein-induced loss of intestinal epithelial stemness contributes to bile duct ligation-induced cholestatic liver injury in mice.

Impaired intestinal barrier function promotes the progression of various liver diseases, including cholestatic liver diseases. The close association of primary sclerosing cholangitis (PSC) with inflammatory bowel disease highlights the importance of the gut-liver axis. It has been reported that bile duct ligation (BDL)-induced liver fibrosis is significantly reduced in C/EBP homologous protein knockout (CHOP-/- ) mice. However, the underlying mechanisms remain unclear. In the current study, we demonstrate that BDL induces striking and acute hepatic endoplasmic reticulum (ER) stress responses after 1 day, which return to normal after 3 days. No significant hepatocyte apoptosis is detected 7-14 days following BDL. However, the inflammatory response is significantly increased after 7 days, which is similar to what we found in human PSC liver samples. BDL-induced loss of stemness in intestinal stem cells (ISCs), disruption of intestinal barrier function, bacterial translocation, activation of hepatic inflammation, M2 macrophage polarization and liver fibrosis are significantly reduced in CHOP-/- mice. In addition, intestinal organoids derived from CHOP-/- mice contain more and longer crypt structures than those from wild-type (WT) mice, which is consistent with the upregulation of stem cell markers (leucine-rich repeat-containing G-protein-coupled receptor 5, olfactomedin 4, and SRY [sex determining region Y]-box 9) and in vivo findings that CHOP-/- mice have longer villi and crypts as compared to WT mice. Similarly, mRNA levels of CD14, interleukin-1ß, tumor necrosis factor-alpha, and monocyte chemotactic protein-1 are increased and stem cell proliferation is suppressed in the duodenum of patients with cirrhosis. CONCLUSION: Activation of ER stress and subsequent loss of stemness of ISCs plays a critical role in BDL-induced systemic inflammation and cholestatic liver injury. Modulation of the ER stress response represents a potential therapeutic strategy for cholestatic liver diseases as well as other inflammatory diseases. (Hepatology 2018;67:1441-1457).

Cholangiocyte-derived exosomal long noncoding RNA H19 promotes cholestatic liver injury in mouse and humans.

Cholestatic liver injury is an important clinical problem with limited understanding of disease pathologies. Exosomes are small extracellular vesicles released by a variety of cells, including cholangiocytes. Exosome-mediated cell-cell communication can modulate various cellular functions by transferring a variety of intracellular components to target cells. Our recent studies indicate that the long noncoding RNA (lncRNA), H19, is mainly expressed in cholangiocytes, and its aberrant expression is associated with significant down-regulation of small heterodimer partner (SHP) in hepatocytes and cholestatic liver injury in multidrug resistance 2 knockout (Mdr2-/- ) mice. However, how cholangiocyte-derived H19 suppresses SHP in hepatocytes remains unknown. Here, we report that cholangiocyte-derived exosomes mediate transfer of H19 into hepatocytes and promote cholestatic injury. Hepatic H19 level is correlated with severity of cholestatic injury in both fibrotic mouse models, including Mdr2-/- mice, a well-characterized model of primary sclerosing cholangitis (PSC), or CCl4 -induced cholestatic liver injury mouse models, and human PSC patients. Moreover, serum exosomal-H19 level is gradually up-regulated during disease progression in Mdr2-/- mice and patients with cirrhosis. H19-carrying exosomes from the primary cholangiocytes of wild-type (WT) mice suppress SHP expression in hepatocytes, but not the exosomes from the cholangiocytes of H19-/- mice. Furthermore, overexpression of H19 significantly suppressed SHP expression at both transcriptional and posttranscriptional levels. Importantly, transplant of H19-carrying serum exosomes of old fibrotic Mdr2-/- mice significantly promoted liver fibrosis (LF) in young Mdr2-/- mice. CONCLUSION: Cholangiocyte-derived exosomal-H19 plays a critical role in cholestatic liver injury. Serum exosomal H19 represents a noninvasive biomarker and potential therapeutic target for cholestatic diseases. (Hepatology 2018).