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The platelet/high-density lipoprotein ratio (PHR) has been identified as a significant indicator of inflammation and a hypercoagulable state, demonstrating a strong link with the severity of nonalcoholic fatty liver disease (NAFLD) and metabolic syndrome (MetS). However, its correlation with hyperuricemia has not yet been documented. This study utilized a cross-sectional design, analyzing data collected from the National Health and Nutrition Examination Survey (NHANES) between 2007 and 2016 in the United States. The platelet/high-density lipoprotein ratio (PHR) was determined by dividing the number of platelets (PLT) by the level of high-density lipoprotein cholesterol (HDL-C). We employed multivariable logistic regression analyses, generalized additive models, and subgroup analyses to investigate the correlation between PHR and hyperuricemia. The study revealed a hyperuricemia prevalence of 18.56%. Analysis indicated a significant positive correlation between PHR and the risk of hyperuricemia (OR 1.11, 95% CI 1.08, 1.14). This correlation remained consistent across different subgroups including age, ethnicity, gender, and body mass index (BMI). Smooth curve fitting demonstrated a saturation effect between PHR and the risk of hyperuricemia. PHR is positively correlated with hyperuricemia and may serve as a novel biomarker for predicting the onset of this condition. Additionally, targeted interventions to improve PHR might help reduce the incidence of hyperuricemia. [ABSTRACT FROM AUTHOR]

Composed of obesity and lipid parameters, the cardiometabolic index (CMI) has emerged as a novel diagnostic tool. Originally developed for diabetes diagnosis, its application has expanded to identifying patients with cardiovascular diseases, such as atherosclerosis and hypertension. However, the relationship between CMI and non-alcoholic fatty liver disease (NAFLD) and liver fibrosis in the US population remains unclear. This cross-sectional study analyzed data from the National Health and Nutrition Examination Survey (NHANES) spanning 2017–2020, involving 2996 participants aged 20 years or older. Vibration controlled transient elastography using a FibroScan® system (model 502, V2 Touch) with controlled attenuation parameter measurements identified NAFLD at a threshold of ≥ 274 dB/m, while liver stiffness measurement (LSM) results (median, ≥ 8.2 kPa) indicated fibrosis. A multifactorial logistic regression model explored the relationship between CMI and NAFLD and fibrosis. The effectiveness of CMI in detecting NAFLD and liver fibrosis was assessed through receiver operating characteristic curve analysis. Controlling for potential confounders, CMI showed a significant positive association with NAFLD (adjusted OR = 1.44, 95% CI 1.44–1.45) and liver fibrosis (adjusted OR = 1.84, 95% CI 1.84–1.85). The Areas Under the Curve for predicting NAFLD and fibrosis were 0.762 (95% CI 0.745 ~ 0.779) and 0.664(95% CI 0.633 ~ 0.696), respectively, with optimal cut-off values of 0.462 and 0.527. There is a positive correlation between CMI and NAFLD and fibrosis, which is a suitable and simple predictor of NAFLD and fibrosis. [ABSTRACT FROM AUTHOR]

This study aimed to screen differentially expressed genes (DEGs) involved in the influence of antiangiogenic therapy on myeloid-derived suppressor cell (MDSC) infiltration and investigate their mechanisms of action. Data on DEGs after the action of antiangiogenic drugs in a pan-cancer context were obtained from the Gene Expression Omnibus (GEO) database. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed using the clusterProfiler package in R software. Single-sample gene set enrichment analysis was performed using the gene set variation analysis package to evaluate the levels of immune cells and the activity of immune-related pathways. The relationships of DEGs with the infiltration levels of MDSCs and specific immune cell subpopulations were investigated via gene module analysis. The top 10 key genes were subsequently obtained from PPI network analysis using the cytoHubba plugin of the Cytoscape platform. When the DEGs of the four datasets were intersected, a DEG in the intersection of three datasets and 12 DEGs in the intersection of two datasets were upregulated, and 28 DEGs in the intersection of two datasets were downregulated. GO and KEGG pathway enrichment analyses revealed that the DEGs were associated with multiple important signaling pathways closely related to tumor onset and development, including cell differentiation, cell proliferation, the cell cycle, and immune responses. Most downregulated genes in lung adenocarcinoma (LUAD) were positively correlated with MDSC expression. Only MGP was negatively correlated; the correlation between CACNG6 and MDSC expression was statistically insignificant. In lung squamous cell carcinoma (LUSC), the relationships of PMEPA1, PCDH7, NEURL1B, and CACNG6 with MDSC expression were statistically insignificant; MGP was negatively correlated with MDSC expression. The top 10 key genes with the highest degree scores obtained using the cytoHubba plugin of Cytoscape were AURKB, RRM2, BUB1, NUSAP1, PRC1, TOP2A, NCAPH, CENPA, KIF2C, and CCNA2. Most of these genes were upregulated in LUAD and associated with immune cell infiltration and prognosis in tumors. An analysis of the relationships between DEGs and infiltration by other specific immune cells revealed the presence of consistent patterns in the downregulated genes, which exhibited positive correlations with the levels of Th2 cells, γδ T cells, and CD56dim NK cells, and negative correlations with other infiltrating immune cells. Antiangiogenic therapy may regulate MDSC infiltration through multiple important signaling pathways closely associated with tumor onset and development, such as cell differentiation, cell proliferation, the cell cycle, and immune responses. Antiangiogenic drugs may exert effects by affecting various types of infiltrating cells associated with immune suppression. [ABSTRACT FROM AUTHOR]

Summary: The well-known impact of ovarian endometriosis on female quality of life and the established role of lncRNA LINC01465 in ovarian cancer pathogenesis have been extensively documented; however, the relationship between LINC01465 and ovarian endometriosis is still not clear. This study seeks to explore the potential involvement of LINC01465 in the disease. The study analyzed a sample of 80 endometriosis patients and 80 healthy women. The expression of LINC01465 was measured in ectopic and eutopic endometrial tissues through RT-qPCR. The diagnostic potential of serum LINC01465 levels was evaluated using ROC curve analysis, and the patients were followed up for 3 years after treatment to monitor recurrence. The results revealed that the expression of LINC01465 was significantly lower in ectopic endometrial tissues in comparison to paired eutopic tissues for most of the patients. No correlation was found between the patient's age or lifestyle and serum LINC01465 levels. After treatment, the serum LINC01465 level increased, and patients who experienced recurrence had significantly lower levels compared to those who did not. In conclusion, the study findings suggest that the downregulation of LINC01465 plays a role in the pathogenesis of ovarian endometriosis and may serve as a diagnostic and prognostic biomarker for the disease. [ABSTRACT FROM AUTHOR]

Using a unique dataset of publicly listed companies in China, we show that the collaborative environmental governance between the central and local governments reduces the effect of local enforcement of regulations on firms' environmentally responsible behaviors. This is consistent with the fact that the Chinese central government uses a command-and-control type of regulations under which the local governments bear the full cost of enforcing the regulations. The local governments do not have the incentive to override the central supervision and therefore, simply lower their standard of enforcement and comply with the central supervision. However, this finding mainly reflects the results from the state-owned enterprises. For the private firms, the central supervision instead strengthens the impact of local enforcement. The heterogeneous results can be explained by the fact that the private firms are more financially constrained compared to the state-owned enterprises. They have the incentives to avoid the costs of complying with the regulations by paying a fine or colluding with the local regulators. The central supervision reduces the asymmetric information and increases the non-compliant firms' chance to get caught for violations or collusion. This explains why once the central government intervenes, those private firms have to improve their environmentally responsible behaviors. [ABSTRACT FROM AUTHOR]

Resilience is the basic attribute of rural regional systems and plays an important role in promoting rural revitalization and high-quality development. Taking 109 administrative villages in Yongchang County, Hexi Corridor, China, as evaluation units, this paper constructed a comprehensive evaluation indicator system of oasis rural resilience from ecological, economic and social dimensions, which comprehensively measures the rural resilience level. We selected typical sample zones, deeply analyzed the differences of rural resilience in "desert-oasis ecotone, oasis core area, oasis-desert-steppe ecotone" and revealed the formation mechanism, and proposed the differentiated oasis rural resilience optimization governance path. The results show that: (1) The mathematical agglomeration characteristics of oasis rural resilience are significant, mainly at high and medium levels. The ecological resilience is relatively high, followed by economic resilience, and social resilience is the lowest; (2) the spatial difference of oasis rural resilience is significant, showing the spatial characteristics of decreasing from oasis core area to oasis edge area. The rural resilience level of the three transects is the oasis core area > oasis-desert-steppe ecotone > desert-oasis ecotone; (3) ecological environment is the leading condition and core factor affecting the resilience of oasis villages. In addition, it is also affected by many factors such as the market economy and government regulation. The improvement of the resilience level of oasis villages requires multiple subjects to participate in the process of rural governance and promote the sustainable development of oasis villages according to local conditions. [ABSTRACT FROM AUTHOR]

The rainy seasons in the Yangtze River valley (called Meiyu) and North China represent two main stages with the northward advance of the East Asian summer monsoon. This study investigates the precipitation prediction skills between these two rainy seasons using the S2S hindcast data from the European Centre for Medium-Range Weather Forecast (ECMWF) during 2002–2021. Meiyu exhibits higher precipitation forecast skill compared to the rainy season in North China. In particular, the forecast skill is more pronounced in the southeast region during the Meiyu, while it has negative performance in central regions of the rainy season in North China. Precipitation patterns during the Meiyu are strongly influenced by the single-blocking system in the high latitude extending from the east of Lake Baikal to the Sea of Okhotsk, as well as the subtropical high at 500 hPa geopotential height in the low latitude. For the rainy season in North China, anomalies in the 500 hPa geopotential height over northeast China has a significant impact on the precipitation according to reanalysis data. The forecast skill of precipitation differs between the two rainy seasons, as well as their associared biases. The model biases are attribute to both circulation simulation and its influence on precipitation. Specifically, the prediction skills of circulation in the low latitudes are high during the Meiyu, and the relationship between circulation and precipitation is well captured. However, the prediction of circulations in the high latitude shows lower skill. During the rainy season in North China, the prediction skills for circulation in key areas are relatively high, but the relationship between circulation in key areas and precipitation is not captured, or may even exhibite an opposite relationship. Meanwhile, the model circulations at different latitudes have different responses to the El Niño state, with more biases observed in the high latitudes. In summary, the decline in prediction skills with the northward advance of the East Asian summer monsoon emphasizes the crucial role of predictability in the high latitudes. [ABSTRACT FROM AUTHOR]

Purpose: Patients with chronic hepatitis B (CHB) remain at risk for hepatocellular carcinoma during antiviral therapy. We aimed to clarify the values of alpha-fetoprotein (AFP), lectin-reactive fraction of AFP (AFP-L3), and des-γ-carboxyprothrombin (DCP) for early warning of HCC. Methods: A total of 1348 CHB patients received antiviral therapy and follow-up every 26 weeks. Eighty-four patients with HCC were age-, sex-, and cirrhosis-matched with 168 controls. AFP, AFP-L3, and DCP were compared between the groups from 104 weeks before HCC diagnosis (− 104 w) to the time of diagnosis (0 w). Results: Of the 84 HCC patients, 60 (71.4%) had early-stage HCC, AFP increased from − 26 w, and AFP-L3 and DCP increased from − 78 w. However, levels were unchanged in controls. ΔAFP, ΔAFP-L3, and ΔDCP showed similar abilities for predicting HCC (P > 0.05). Receiver operating characteristic curve analysis showed that AFP had better diagnostic performance for HCC than AFP-L3, DCP, or their combination. The cut-off values of AFP, AFP-L3, and DCP were 5.3 ng/mL, 1.05%, and 31.5 mAU/mL, respectively. Notably, lower AFP values were required to diagnose HCC in patients with detectable HBV DNA (4.1 ng/mL) or elevated alanine aminotransferase (5.2 ng/mL). Conclusions: Changes in AFP, AFP-L3, and DCP can help to predict HCC in CHB patients receiving antiviral therapy. A lower AFP value is needed to diagnose HCC, especially in patients with detectable HBV DNA or elevated alanine aminotransferase. [ABSTRACT FROM AUTHOR]

We describe the contrast-enhanced thoracic computed tomography (CT), magnetic resonance imaging (MRI), and 18F-FDG PET/CT findings. Perivascular epithelioid cell tumors are rare mesenchymal tumors, that have been recognized in recent years due to their specific morphological and immunohistochemical characteristics. Axial (B-D), coronal (E-G), and sagittal (H-J) views of selected PET, NECT, and fused PET/CT images revealing a mass with mild 18F-FDG uptake (SUVmax 3.1) Graph: Figure 5The specimen was a gray-yellowish solid tumor (A). [Extracted from the article]

Adjusting antiplatelet strategies after antiplatelet-associated gastrointestinal bleeding (GIB) is a complex clinical challenge. To assess the risk of outcomes at different times of resumption of antiplatelet therapy in an attempt to find the optimal time to resume therapy. The study analyzed consecutive patients with antiplatelet-associated GIB from Beijing Friendship Hospital Information System between October 2019 and June 2022. The primary outcomes were recurrent bleeding, major adverse cardiovascular and cerebrovascular events (MACE), and all-cause death. Multivariate-adjusted Cox proportional hazards models were used to evaluate the risks of these outcomes. The receiver operating characteristic curve was used to find the optimal time to resume treatment. Of the 617 patients with GIB after antiplatelet therapy successfully followed up, the median follow‐up was 246 (interquartile range: 120–466) days, most patients (87.36%) interrupted therapy after GIB and 45.22% resumed within 90 days, of which 35.13% resumed within 7 days and 64.87% resumed after 7 days. Resumption therapy had a low risk of recurrent bleeding (uninterrupted as a reference: HR 0.32, 95% CI 0.15–0.67, p = 0.003), MACE (no resumption as a reference: HR 0.66, 95% CI 0.45–0.98, p = 0.037), and all-cause death (no resumption as a reference: HR 0.18, 95% CI 0.08–0.40, p < 0.001). And resuming therapy within 7 days had a lower risk of MACE (HR 0.18, 95% CI 0.08–0.44, p < 0.001) than after 7 days without a significantly higher risk of re-bleeding. The optimal time point for resuming therapy in this study was 8.5 days. Resuming antiplatelet therapy after GIB provides better clinical benefits compared to discontinued and uninterrupted therapy, especially compared with resuming after 7 days, resuming within 7 days is associated with a lower risk of MACE and a less significant increased risk of recurrent bleeding, leading to a higher net clinical benefit. China Clinical Trial Registration: ChiCTR2200064063. [ABSTRACT FROM AUTHOR]

Hydroxyapatite (HAP) is a promising adsorbent for immobilizing heavy metals in soil and water. However, the preparation and modification of HAP from pure chemicals increases its cost and limits its large-scale practical application. In this study, a hydroxyapatite-based adsorbent (HAPPT) was prepared from phosphate tailing produced in the phosphorus industry to sequester Pb, Cd and Zn from solution. The results showed that HAPPT was composed of HAP and MgO, with a surface area of 27.74 m2/g. The kinetics studies showed that most Pb and Cd were removed from the initial solution in 4 h and the adsorption of Zn increased with increasing contact time. Metals presented higher adsorption capacities at 35 °C than that at 25 °C. The adsorption isotherms showed that HAPPT presented high adsorption capacities for Pb, Cd and Zn in mono-metal solutions. The adsorption capacity of Cd at pH 6 was higher than that at pH 3, but the adsorption for Pb and Zn was similar at both pHs. HAPPT has selectivity for Pb in Pb–Cd-Zn multi-metals solution, and competitive adsorption reduced the adsorption quantity by 53%, 93% and 79% for Pb, Cd and Zn, respectively. The combined results of TEM-EDS, XRD and XPS showed that Pb was immobilized by forming phosphates due to the dissolution of HAP, whereas Cd and Zn were immobilized by forming hydroxide precipitates resulting from the function of MgO in HAPPT. The results of this study provided an efficient adsorbent for the removal of heavy metals in solution and provided a new perspective on the recycling of phosphate tailings in the phosphorus industry. [ABSTRACT FROM AUTHOR]

The Gated Recurrent Unit (GRU) neural network has great potential in estimating and predicting a variable. In addition to radar reflectivity (Z), radar echo-top height (ET) is also a good indicator of rainfall rate (R). In this study, we propose a new method, GRU_Z-ET, by introducing Z and ET as two independent variables into the GRU neural network to conduct the quantitative single-polarization radar precipitation estimation. The performance of GRU_Z-ET is compared with that of the other three methods in three heavy rainfall cases in China during 2018, namely, the traditional Z-R relationship (Z=300R1.4), the optimal Z-R relationship (Z=79R1.68) and the GRU neural network with only Z as the independent input variable (GRU_Z). The results indicate that the GRU_Z-ET performs the best, while the traditional Z-R relationship performs the worst. The performances of the rest two methods are similar. To further evaluate the performance of the GRU_Z-ET, 200 rainfall events with 21882 total samples during May–July of 2018 are used for statistical analysis. Results demonstrate that the spatial correlation coefficients, threat scores and probability of detection between the observed and estimated precipitation are the largest for the GRU_Z-ET and the smallest for the traditional Z-R relationship, and the root mean square error is just the opposite. In addition, these statistics of GRU_Z are similar to those of optimal Z-R relationship. Thus, it can be concluded that the performance of the GRU_Z-ET is the best in the four methods for the quantitative precipitation estimation. [ABSTRACT FROM AUTHOR]

Aberrant activation of TGF-β signaling plays a pivotal role in cancer metastasis and progression. However, molecular mechanisms underlying the dysregulation of TGF-β pathway remain to be understood. Here, we found that SMAD7, a direct downstream transcriptional target and also a key antagonist of TGF-β signaling, is transcriptionally suppressed in lung adenocarcinoma (LAD) due to DNA hypermethylation. We further identified that PHF14 binds DNMT3B and serves as a DNA CpG motif reader, recruiting DNMT3B to the SMAD7 gene locus, resulting in DNA methylation and transcriptional suppression of SMAD7. Our in vitro and in vivo experiments showed that PHF14 promotes metastasis through binding DNMT3B to suppress SMAD7 expression. Moreover, our data revealed that PHF14 expression correlates with lowered SMAD7 level and shorter survival of LAD patients, and importantly that SMAD7 methylation level of circulating tumor DNA (ctDNA) can potentially be used for prognosis prediction. Together, our present study illustrates a new epigenetic mechanism, mediated by PHF14 and DNMT3B, in the regulation of SMAD7 transcription and TGF-β-driven LAD metastasis, and suggests potential opportunities for LAD prognosis. [ABSTRACT FROM AUTHOR]

Introduction: Compared with traditional fundus examination techniques, ultra-widefield fundus (UWF) images provide 200° panoramic images of the retina, which allows better detection of peripheral retinal lesions. The advent of UWF provides effective solutions only for detection but still lacks efficient diagnostic capabilities. This study proposed a retinal lesion detection model to automatically locate and identify six relatively typical and high-incidence peripheral retinal lesions from UWF images which will enable early screening and rapid diagnosis. Methods: A total of 24,602 augmented ultra-widefield fundus images with labels corresponding to 6 peripheral retinal lesions and normal manifestation labelled by 5 ophthalmologists were included in this study. An object detection model named You Only Look Once X (YOLOX) was modified and trained to locate and classify the six peripheral retinal lesions including rhegmatogenous retinal detachment (RRD), retinal breaks (RB), white without pressure (WWOP), cystic retinal tuft (CRT), lattice degeneration (LD), and paving-stone degeneration (PSD). We applied coordinate attention block and generalized intersection over union (GIOU) loss to YOLOX and evaluated it for accuracy, sensitivity, specificity, precision, F1 score, and average precision (AP). This model was able to show the exact location and saliency map of the retinal lesions detected by the model thus contributing to efficient screening and diagnosis. Results: The model reached an average accuracy of 96.64%, sensitivity of 87.97%, specificity of 98.04%, precision of 87.01%, F1 score of 87.39%, and mAP of 86.03% on test dataset 1 including 248 UWF images and reached an average accuracy of 95.04%, sensitivity of 83.90%, specificity of 96.70%, precision of 78.73%, F1 score of 81.96%, and mAP of 80.59% on external test dataset 2 including 586 UWF images, showing this system performs well in distinguishing the six peripheral retinal lesions. Conclusion: Focusing on peripheral retinal lesions, this work proposed a deep learning model, which automatically recognized multiple peripheral retinal lesions from UWF images and localized exact positions of lesions. Therefore, it has certain potential for early screening and intelligent diagnosis of peripheral retinal lesions. [ABSTRACT FROM AUTHOR]

Vanadium diselenide (VSe2), with large interlayer spacing, is a promising anode material for sodium-ion batteries (SIBs). However, due to the existence of a conversion reaction, VSe2 will encounter a huge volume change during charging/discharging, resulting in electrode pulverization. On the other hand, VSe2 nanosheets are prone to disordered stacking during the deintercalation of sodium ions, affecting the next intercalation. Therefore, VSe2 embedded into a three-dimensional N-doped carbon framework (VSe2@3D-CN), was constructed to solve the above problems. Firstly, the three-dimensional carbon framework, with void spaces, can maintain the structural integrity of the electrode during charging/discharging, improving cycle performance. Secondly, the structure that VSe2 nanosheets are embedded in a three-dimensional carbon framework can avoid disordered stacking for VSe2, which can maintain an open insertion channel of sodium ions. Thirdly, nitrogen doping can increase the active sites, enhancing the absorption of sodium ions in the carbon layer and thus obtaining superior rate performance. Based on the synergistic effect of the above modification strategies, outstanding electrochemical performance was obtained. After charging and discharging 150 times at a current density of 200 mA/g, the specific capacity of VSe2@3D-CN is up to 465 mAh/g. Besides, the sodium storage model of VSe2@3D-CN has been built via ex situ XPS and ex situ HRTEM tests, which provides an important reference for improving cycle performance. [ABSTRACT FROM AUTHOR]

Many neuroimaging studies have reported that stroke induces abnormal brain activity. However, little is known about resting-state networks (RSNs) and the corresponding white matter changes in stroke patients with hemiplegia. Here, we utilized functional magnetic resonance imaging (fMRI) to measure neural activity and related fibre tracts in 14 ischaemic stroke patients with hemiplegia and 12 healthy controls. Fractional amplitude of low-frequency fluctuations (fALFF) calculation and correlation analyses were used to assess the relationship between regional neural activity and movement scores. Tractography was performed using diffusion tensor imaging (DTI) data to analyse the fibres passing through the regions of interest. Compared with controls, stroke patients showed abnormal functional connectivity (FC) between some brain regions in the RSNs. The fALFF was increased in the contralesional parietal lobe, with the regional fALFF being correlated with behavioural scores in stroke patients. Additionally, the passage of fibres across regions with reduced FC in the RSNs was increased in stroke patients. This study suggests that structural remodelling of functionally relevant white matter tracts is probably an adaptive response that compensates for injury to the brain. [ABSTRACT FROM AUTHOR]

Cellular c-FLIP prevents apoptosis mediated by death receptor through inhibiting activation of caspase-8. Therefore, when c-FLIP is downregulated or eliminated, caspase-8 activation is promoted, and death receptor ligand-induced apoptosis is activated. It was reported that triptolide (TPL) sensitized tumor cells to TNF-α-induced apoptosis by blocking TNF-α-induced activation of NF-κB and transcription of c-IAP1 and c-IAP2. However, the effect of TPL on basal c-FLIP expression was not understood. In this study, we found that the combination of TNF-α and TPL accelerated apoptosis in human hepatocellular carcinoma cells and TNF-α-induced elevated as well as basal level of FLIPS protein were downregulated by TPL. Additionally, we demonstrated that the basal level of FLIPS in Huh7 cells was continuously downregulated following the incubation of TPL and downregulated more when dosage of TPL for treatment was increased. Subsequently, we showed that TPL reduced FLIPS level in a transcription- and degradation-independent mechanism. Our findings suggest that TPL induces loss of FLIPS at the post-transcriptional level independently of proteasome-mediated pathway, an additional mechanism of TPL sensitizing cancer cells to TNF-α-induced apoptosis. [ABSTRACT FROM AUTHOR]

Background: The efficacy of nucleos(t)ide analogs (NAs) in non-cirrhotic chronic hepatitis B (CHB) patients is well-established. However, their impact on complications of portal hypertension in advanced chronic liver disease (ACLD) is less well characterized. Methods: MEDLINE/PubMed, EMBASE, Web of Science, Cochrane Central Register of Controlled Trials, and abstracts of major international hepatology meetings were searched for publications from Jan 1, 1995 to Nov 30, 2021. Randomized control trials and observational studies reporting the efficacy of NAs in ACLD patients were eligible. Pooled risk ratios (RRs) for outcomes of interest were calculated with a random-effect or fixed-effect model, as appropriate. Results: Thirty-nine studies including 14,212 ACLD patients were included. NA treatment was associated with reduced risks of overall hepatic decompensation events (RR, 0.51; 95% confidence interval [CI]: 0.37–0.71), such as variceal bleeding (RR, 0.44; 95% CI: 0.26–0.74) and ascites (RR, 0.10; 95% CI: 0.01–1.59), on a trend-wise level. Moreover, the risks of hepatocellular carcinoma (HCC) (RR, 0.48; 95% CI: 0.30–0.75) and liver transplantation/death (RR, 0.36; 95% CI: 0.25–0.53) were also reduced by NA treatment and the first-line NAs were superior to non-first-line NAs in improving these outcomes (RR, 0.85; 95% CI: 0.75–0.97 and RR, 0.85; 95% CI: 0.73–0.99, respectively). Conclusion: NA therapy lowers the risk of portal hypertension-related complications, including variceal bleeding, HCC, and liver transplantation/death. [ABSTRACT FROM AUTHOR]

In this study, we aimed to synthesize magnetically well-dispersed nanosensors for detecting dissolved oxygen (DO) in water, and explore their biological applications. Firstly, we synthesized two kinds of magnetic nanoparticle with average sizes of approximately 82 nm by one-step emulsion polymerization: polystyrene magnetic nanoparticles (Fe3O4@Os1-PS) and polymethylmethacrylate magnetic nanoparticles (Fe3O4@Os1-PMMA). Both types of nanoparticle present good dispersibility and fluorescence stability. The nanoparticles could be used as oxygen sensors that exhibited a high DO-sensitivity response in the range 0-39.30 mg/L, with a strong linear relationship. The nanoparticles have good magnetic properties, and so they could be recycled by magnet for further use. Recovered Fe3O4@Os1-PS still presented high stability after continued use in oxygen sensing for one month. Furthermore, Fe3O4@Os1-PS was employed for detecting the bacterial oxygen consumption of Escherichia coli (E-coli) to monitor the metabolism of bacteria. The results show that Fe3O4@Os1-PS provide high biocompatibility and non-toxicity. Polystyrene magnetic nanoparticles therefore present significant potential for application in biological oxygen sensing. [ABSTRACT FROM AUTHOR]

Further validation was performed by treating HCC cell lines (Hep3B and Huh7) with a combination of cabozantinib and the EGFR inhibitor WZ3146, which is identified from compound screening. We tested the synergy between WZ3146 and c-MET inhibitor (capmatinib), c-RET inhibitor (GSK3179106), c-KIT inhibitor (dasatinib), TIE2 inhibitor (Tie 2 kinase inhibitor) or AXL inhibitor (dubermatinib), respectively. As mentioned above, WZ3146 was developed as a mutant-selective EGFR inhibitor against EGFR T790M[8], whereas in our study we observed that WZ3146 also obviously inhibited the wild-type EGFR (Fig. To validate whether EGFR signaling could be responsible for the limited response to cabozantinib, we established I EGFR i -knockdown cell line. shRNA-mediated EGFR knockdown in Hep3B cells sensitized them to cabozantinib, indicating a causal relationship between EGFR signaling and sensitivity to cabozantinib (Fig. [Extracted from the article]

Purpose: This study aimed to explore whether infertility duration has an impact on the sexual function and mental health of men from infertile couples. Methods: We conducted a case–control study of 558 men from infertile couples, and the participants were divided into four groups based on their infertility duration: group I: ≤ 2 years; group II: 2–5 years; group III: 5–8 years; and group IV: > 8 years. Sexual function and mental disorders were measured using the International Index of Erectile Function-15 (IIEF-15), Premature Ejaculation Diagnostic Tool (PEDT), Generalized Anxiety Disorder scale (GAD-7), and Patient Health Questionnaire (PHQ-9) separately. Results: As the years of infertility duration increase, the total IIEF-15 score and four domains (sexual desire, orgasmic function, erectile function, and intercourse satisfaction) significantly decrease (p < 0.05). The PEDT score gradually increases significantly (p < 0.05). Increased infertility duration is an independent risk factor for erectile dysfunction and premature ejaculation (p < 0.05). However, increased infertility duration is not a risk factor for depression and anxiety (p > 0.05). Conclusions: Our study is the first time to use the infertility duration as an independent variable and group this variable to analyze its impact on the sexual function and mental health of men from infertile couples comprehensively and systematically. The increased infertility duration is an independent risk factor for the occurrence of sexual dysfunction but not for mental disorders. In the process of infertility treatment, sexual health and mental health cannot be ignored, especially for patients with prolonged infertility. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to explore whether the coronavirus disease (COVID-19) vaccination of both partners in infertile couples, different types of COVID-19 vaccines, and the interval between complete vaccination and oocyte retrieval or embryo transfer (ET) affect the quality of embryos and pregnancy rates in in vitro fertilization (IVF). Methods: This was a prospective cohort study, comprising 735 infertile couples conducted between December 6, 2021, and March 31, 2022, in a single university hospital-based IVF center. The patients were divided into different groups according to the vaccination status of both partners in infertile couples, type of vaccine, and interval between complete vaccination and IVF treatment. The embryo quality and pregnancy rates were compared among different groups. Results: The results showed that embryo quality and pregnancy rates had no significant differences among different groups. The multivariate regression model showed that the vaccination status of both infertile couples, types of vaccines, and intervals had no significant effects on the clinical pregnancy rate. Conclusions: The vaccination status of both partners in infertile couples, different types of vaccines, and time intervals have no effect on embryo quality and pregnancy rates in IVF. This is the first study to compare the vaccination status of both partners in infertile couples and the impact of different vaccine types on pregnancy rates and embryo quality in detail. Our findings provide evidence of vaccine safety for infertile couples wishing to undergo IVF treatment. This evidence is crucial for decision-making by clinicians and policymakers involved in IVF cycles. [ABSTRACT FROM AUTHOR]

The rural social space quality is an important indicator to measure the living standard and thinking ideas and so forth of rural residents in a certain region. In this paper, 213 administrative villages in Longxi County of the Loess Hilly Area, China are taken as evaluation units to construct the evaluation model of the rural social space quality. This paper deeply analyzed the variation patterns and their formation mechanism of the rural social space quality at a village scale, and proposed a governance model based on the rural social space quality. The results show that: (1) the social space quality levels of individual administrative villages show a gradually decreasing trend from the township seats to outward. The eastern part of Longxi County has a relatively high education level and living standard, and the western part has a relatively high population stability level and income level. (2) The rural social space quality is mainly in a ring structure, supplemented by the interlaced structure. The core area is the towns and their surrounding areas, while the transition area, marginal area, and other areas are expanded around the core area. (3) Social forces and spatial effects jointly shape the variation of the rural social space quality. Social organizations provide a driving force for the allocation of elements, and interweaving with the spatial effects lead to the differences in the social space quality. (4) The governance models of the rural social space quality are constructed based on the principles of retaining the rural "people", optimizing the rural "land", and developing the rural "industry", so as to improve the rural centripetal force, core force, inner thrust, and source power. [ABSTRACT FROM AUTHOR]

In this study, high-resolution weather research and forecasting (WRF) simulations are used to explore the sensitivity of lake-effect convection over Poyang Lake (PL) to the change of lake surface temperature (LST). A control experiment (CTR) with climate mean LST (303 K) is compared with six sensitivity experiments (CTR−1/2/3K and CTR+1/2/3K) in which the LSTs are set based on the mean LST difference of 6 K between the maximum and minimum. The results show that the CTR experiment reasonably reproduces the lake-effect convection, and the lake-effect convection in sensitivity experiments is significantly influenced by the LST. With the increase of LST, the initiation time of the lake-effect convection is advanced gradually, while the initiation location moves PL from its shore. The lake-effect convection strengthens (weakens) in the increase-temperature CTR+1/2/3K (decrease-temperature CTR−1/2/3K) experiments, but the lake-effect convection does not monotonically strengthen with the LST, for the strongest one occurring in the CTR+1K experiment. The corresponding diagnostic analysis shows that the upward sensible heat flux and latent heat flux over PL increase with the LST, resulting in the enhancement of the lake-land breeze and the enlargement of the convective available potential energy (CAPE). This is the main reason for the changes in the initiation time and location, as well as the intensity of lake-effect convection in different experiments. In addition, the non-monotonous variation of the level of free convection, which is mainly induced by the non-monotonous variation of the lifting condensation level, is responsible for the non-monotonous variation of the lake-effect convection intensity with the LST. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to explore the perceived changes in sexual behaviour during COVID-19 lockdown, anxiety symptoms, and couple relationship of patients with infertility. Methods: We performed an observational cross-sectional study between 20 November 2020 and 15 January 2021. We used stratified analysis of different stress levels and Quality of Marriage Index (QMI) scores to compare the perceived changes in sexual behaviour, anxiety symptoms, and couple relationship. The logistic regression model was performed to assess factors correlated with couples' relationship quality during the lockdown. Furthermore, we performed pathway analyses to assess whether the changes in sexual behaviour, stress level, or psychological anxiety during the lockdown could predict the quality of couple relationship. Results: A total of 940 patients with infertility were included in this study. When we conducted a stratified analysis of the participants, significant differences were found between the changes in their sexual behaviour, stress levels, and couple relationship quality. The logistic regression model showed that sex, anxiety symptoms, decreased sexual satisfaction, sexual activity frequency, and income levels were closely related to couple relationship quality. Pathway analyses indicated that changes in their sexual behaviour, anxiety symptoms, and stress levels could all predict the quality of couple relationship. Conclusions: The perceived changes in sexual behaviour with different stress levels and couple relationship quality showed significant differences. Analysing the related factors that affect the quality of couple relationship, especially in times of crisis, is of great significance as this information can contribute to the improvement of treatment for patients with infertility. [ABSTRACT FROM AUTHOR]

To examine the association of baseline body mass index (BMI) and BMI change with cognitive impairment among older adults in China. The study included data from the Chinese Longitudinal Healthy Longevity Study, a national community-based prospective cohort study from 2002 to 2018. Baseline BMI and BMI change were available for 12,027 adults aged older than 65 years. Cognitive impairment was defined as Chinese version of the Mini Mental State Examination score lower than 18. Multivariable Cox proportional hazard model was used. Among 12,027 participants (mean age was 81.23 years old and 47.48% were male), the proportion of underweight, normal, overweight and obese at baseline was 33.87%, 51.39%, 11.39% and 3.34%, respectively. During an average of 5.9 years' follow-up, 3086 participants (4.35 per 100 person-years) with incident cognitive impairment were identified. Compared with normal weight group, adjusted hazard ratio (AHR) for cognitive impairment was 0.86 (95% CI 0.75–0.99) among overweight group, whereas corresponding AHR was 1.02 (95% CI 0.94–1.10) in underweight and 1.01 (95% CI 0.80–1.28) in obese participants. Large weight loss (< −10%) was significantly associated with an increased risk of cognitive impairment (AHR, 1.42, 95% CI 1.29–1.56), compared to stable weight status group (−5% ~ 5%). In the restricted cubic spline models, BMI change showed a reverse J-shaped association with cognitive impairment. BMI-defined overweight, but not obesity, was associated with a lower risk of cognitive impairment among elderly Chinese adults, while large weight loss was associated with an increased risk. These findings are consistent with weight loss in the prodromal phase of dementia. [ABSTRACT FROM AUTHOR]

Unique restricted access media-magnetic molecularly imprinted polymers (RAM–MMIPs) were prepared as magnetic solid-phase extraction (MSPE) material for florfenicol (FF) and are combined with HPLC–UV to extract FF from fetal bovine serum samples. Under the optimization conditions, the resulting materials had a uniform imprinted layer, acceptable adsorption amounts (22.92 mg/g), rapid binding kinetics (80 min) and satisfactory selectivity. In addition, RAM–MMIPs presented satisfactory recoveries (95.6–102.1%), relative standard deviation (RSD) (2.7–3.9%) and lower limits of detection (LOD) (10.5 μg/L). The method was applied to the real samples. Compared with other reported methods, this method exhibits the advantages of simple, fast and, efficient operation, using a relatively small amount of the RAM–MMIPs adsorbent. The developed method can enrich FF from fetal bovine serum samples. [ABSTRACT FROM AUTHOR]

Background: The increased consumption of plant-based diets has encouraged studies of bone mineral density (BMD). The present systematic review and meta-analysis compared the effects of plant-based and omnivorous diets on BMD. Methods: We searched the Cochrane Library, PubMed, EMBASE, and the Web of Science to July 1, 2020. We used the mean differences (MDs) with 95% CIs to compare group outcomes. We compared the lumbar spine, femoral neck, and whole-body BMDs of those on plant-based and omnivorous diets. We performed subgroup analyses by various clinical characteristics. Two reviewers independently assessed trial quality and extracted data. All statistical analyses were performed using Review Manager version 5.2. Results: A total of 17 cross-sectional studies including 13,888 patients were identified. The pooled results indicated that those on plant-based diets (compared to omnivores) exhibited lower BMDs at the lumbar spine (MD − 0.04; 95% CI − 0.06 to − 0.02; P < 0.0001) and femoral neck (MD − 0.04; 95% CI − 0.05 to − 0.02; P < 0.00001), and a reduced whole-body BMD (MD − 0.03; 95% CI − 0.06 to − 0.01; P = 0.0009). Both vegetarians and vegans exhibited lower lumbar spine, femoral neck, and whole-body BMDs than omnivores. Conclusions: Plant-based diets were associated with lower BMDs than those of an omnivore population. Plant-based diets may compromise overall bone health; prospective research is required. [ABSTRACT FROM AUTHOR]

Background and aims: Antiviral treatment with necleos(t)ide analogues contributes to histological improvement and virologic response in chronic hepatitis B (CHB) patients. However, whether adding pegylated interferon alpha2a (Peg-IFN-α-2a) can help additional clinical benefit, particularly on fibrosis regression was still unknown. Methods: Chronic hepatitis B patients with pre-treatment biopsy-proven Ishak fibrosis score 2, 3 or 4 were randomly assigned to entecavir (ETV) alone or ETV plus Peg-IFN-α-2a (Peg-IFN-α-2a add-on) group (1:2 ratio). Post-treatment liver biopsy was performed at week 78. Fibrosis regression was defined as decrease in Ishak fibrosis score by ≥ 1 stage or predominantly regressive categorized by P–I–R score. Serum HBV DNA levels were assessed at baseline and every 26 weeks, while HBsAg and HBeAg were evaluated at baseline and every 52 weeks. Results: A total of 218 treatment-naive CHB patients were randomly assigned to ETV alone or Peg-IFN-α-2a add-on group. Totals of 155 patients (ETV alone: Peg-IFN-α-2a add-on, 47:108) were included in statistical analysis. Fibrosis regression rates were 68% (32/47) in the ETV alone and 56% (60/108) in Peg-IFN-α-2a add-on group (p = 0.144). Both groups showed a similar trend of virological suppression during the process of 104-week antiviral therapy (p = 0.132). HBeAg or HBsAg loss or seroconversion rates in the ETV alone group were lower than Peg-IFN-α-2a add-on group though without statistical significance. Conclusions: Peg-IFN-α-2a add-on therapy did not yield additional fibrosis regression and virologic response than ETV alone therapy. [ABSTRACT FROM AUTHOR]

In the last few decades, the eutrophication of lakes has been a serious issue in the middle and lower reaches of the Yangtze River watershed. To explore the relationship between lake systems and anthropogenic activities, sediments were collected from the Shuanglong reservoir in the Dianchi watershed in Southwest China. Total nitrogen (TN), total phosphorus (TP), total organic carbon (TOC), and the carbon isotopic ratio (δ13C) were analyzed in sediment cores to reconstruct the effects of natural succession and human activities on the past lacustrine environmental conditions. A reliable chronology of the sediment core was established by using the 210Pb dating technique, which indicated that the age span of the 70-cm sediment core is from the years 1871 to 2011. Above – 31 cm depth in the core, TN, TP, TOC, C/N, and δ13C increased significantly, indicating that eutrophication has occurred since the 1980s. By combining the indicators of δ13C and C/N, it was shown that terrestrial and lacustrine components were the main sources of organic matter (OM) in the reservoir, which was mostly controlled by terrestrial C3 plants and algae. Since the 1980s, increased sewage discharge, fish aquaculture, fertilizer application, population, and economic strength have sped up the eutrophication process, and the eutrophication was further intensified in 2001. [ABSTRACT FROM AUTHOR]

Objectives: We aimed to determine the value of MR-based preoperative nomograms in predicting DNA copy number (CN) subtype in lower grade glioma (LGG) patients. Methods: The overall survival (OS) data were analyzed. MRI data of 170 subjects were retrospectively analyzed. The correlation was explored by univariate and multivariate regression analysis. Results: CN2 subtype was associated with shortest median OS (CN2 subtype vs. others: 46.8 vs. 221.7 months, p < 0.05). The time-dependent receiver operating characteristic for the CN2 subtype was 0.80 (95% CI: 0.74–0.85) for survival at 1 year, 0.80 (95% CI: 0.75–0.85) for survival at 2 years, and 0.77 (95% CI: 0.73–0.83) for survival at 3 years. On multivariate analysis, hemorrhage (OR: 0.118; p < 0.001; 95% CI: 0.037–0.376), poorly defined margin (OR: 4.592; p < 0.001; 95% CI: 1.965–10.730), extranodular growth (OR: 0.247; p = 0.006; 95% CI: 0.091–0.671), and volume ≥ 60 cm3 (OR: 4.734.256; p < 0.001; 95% CI: 2.051–10.924) were associated with CN1 subtype (AUC: 0.781). Proportion CE tumor (OR: 5.905; p = 0.007; 95% CI: 1.622–21.493), extranodular growth (OR: 9.047; p = 0.001; 95% CI: 2.349–34.846), width ≥ median (OR: 0.231; p = 0.049; 95% CI: 0.054–0.998), and depth ≥ median (OR: 0.192; p = 0.023; 95% CI: 0.046–0.799) were associated with CN2 subtype (AUC: 0.854). Necrosis/cystic (OR: 6.128; p = 0.007; 95% CI: 1.635–22.968), hemorrhage (OR: 5.752; p = 0.002; 95% CI: 1.953–16.942), poorly defined margin (OR: 0.164; p < 0.001; 95% CI: 0.063–0.427), and volume ≥ median (OR: 4.422; p < 0.001; 95% CI: 1.925–10.160) were associated with CN3 subtype (AUC: 0.808). All three nomograms showed good discrimination and calibration. Decision curve analysis supported that all nomograms were clinically useful. The average accuracy of the tenfold cross-validation was 0.680 (CN1), 0.794 (CN2), and 0.894 (CN3), respectively. Conclusions: The shortest OS was observed in patients with CN2 subtype. This preliminary radiogenomics analysis revealed that the MR-based preoperative nomograms provide individualized prediction of DNA copy number subtype in LGG patients. Key Points: • This preliminary radiogenomics analysis of LGG revealed that the MR-based preoperative nomograms provide individualized prediction of DNA copy number subtype in LGG patients. • The AUC for the ROC curve was 0.781 for CN1 subtype, 0.854 for CN2 subtype, and 0.808 for CN3 subtype. Decision curve analysis supported that all nomograms were clinically useful. • The sensitivity was 0.779 (CN1), 0.731 (CN2), and 0.851 (CN3), respectively. The specificity was 0.664 (CN1), 0.872 (CN2), and 0.625 (CN3), respectively. And the accuracy was 0.717 (CN1), 0.849 (CN2), and 0.692 (CN3), respectively. [ABSTRACT FROM AUTHOR]

A zirconium-based metal–organic framework (DUT-69) was fabricated via a hydrothermal synthesis for U(VI) removal in aqueous solutions. Experimental results showed that the maximum adsorption capacity for U(VI) was 362.32 mg·g−1 at 303 K, pH = 6 and initial U(VI) concentration of 80 mg L−1. The adsorption process fit well with the pseudo-second-order kinetic and Langmuir models. Various characterizations indicated that complexation interactions was the central adsorption mechanism and electrostatic was the secondary. The carboxyl, Zr–O, and C–S bonds in the framework participated in the adsorption process. Reusability experiments showed that 80.34% adsorption rate could be maintained after 5 cycles. [ABSTRACT FROM AUTHOR]

Stroke is one of the highest incidence neurological disorder with great morbidity and mortality rate. The secondary neuroinflammation contributed by microglial activation is a consequential response observed in the pathogenesis of stroke. High-mobility group box 1, a non-histone nuclear protein, interacts with immune cells, such as microglia, and leads to a cascade amplification of the secondary neuroinflammatory responses, which are related to neuronal damage later. Melatonin is a neurohormone, well-known as its anti-oxidative and anti-inflammatory effects. However, until now, more findings are required for better understanding about anti-inflammatory effect of melatonin on HMGB1 and HMGB1-triggered pathway in LPS-induced microglial activation. Melatonin effect on the viability of BV2 microglial cells was measured by CCK-8 assay; mRNA levels of HMGB1 and other inflammatory cytokines were determined by quantitative real-time polymerase chain reaction assay or enzyme-linked immunosorbent assays; the protein expression levels of TLR4/MyD88/NF-κB and SIRT1 were detected by Western blot, and HMGB1 translocation and release from BV2 microglial cells were examined by immunofluorescence assay. The results of this study demonstrated that melatonin suppressed LPS-triggered BV2 microglial activation-mediated inflammation by inhibiting high expression and release of HMGB1 and moderating the activation of subsequent TLR4/MyD88/NF-κB signaling pathway, which was activated by SIRT1 elevation. Furthermore, LPS-induced expression of pro-inflammatory cytokines (i.e., TNF-α, IL-6, and IL-1β) was notably reversed by melatonin pre-treatment. In summary, our findings suggest that melatonin may act as a promising therapeutic agent for reducing post-stroke neuroinflammation by targeting HMGB1 and the subsequent signaling axis. [ABSTRACT FROM AUTHOR]

EG1 from Volvariella volvacea is a processive endoglucanase belonging to glycoside hydrolase family 5. The impacts of cotton linter pulp characteristics, such as degree of polymerization (DP), crystallinity, and the initial cellulose-reducing ends, on the processivity of EG1 were investigated. Three commercial cotton linter pulp with different DP were used in present study. Ball milling was used to alter the crystallinity and DP of cellulose. The results indicate that the crystallinity has the most significant impact on enzyme processivity followed by initial cellulose-reducing ends. Whereas the DP indirectly affects the enzymatic hydrolysis and influenced by the pulp preparation method and conditions. The initial cellulose-reducing ends also affect enzyme adsorption but their impact is not obvious when the crystallinity is very low. These results also demonstrate the endo- and exo-action are both exist for EG1. The processive exo-action can start from the newly created cellulose-reducing ends by endo-action as well as the initial cellulose-reducing ends. The contribution of initial cellulose-reducing ends is affected by its quantity and cellulose crystallinity. A plausible action mode for EG1 is also proposed. [ABSTRACT FROM AUTHOR]

Gut microbiota modulation by a probiotic is a novel therapy for hypercholesterolemia mitigation. This study initially investigated the potential hypocholesterolemic effect of Bacillus sp. DU-106 in hypercholesterolemic rats and explored its potential relation with gut microbiota. Sprague–Dawley rats received a high-fat diet, or a high-fat diet supplemented with 7.5 × 109 and 1.5 × 1010 CFU/kg bw/day Bacillus sp. DU-106 (low-dose and high-dose groups). At the end of 9 weeks, Bacillus sp. DU-106 treatment significantly decreased the body weight, liver index, and total cholesterol. 16S rRNA sequencing showed that Bacillus sp. DU-106 intervention significantly increased bacterial richness and particularly increased the genus abundance of Turicibacter, Acinetobacter, Brevundimonas, and Bacillus and significantly decreased the abundance of Ralstonia. Metabolomic data further indicated that the supplementation of Bacillus sp. DU-106 remarkably changed the gut metabolic profiles of hypercholesterolemic rats and, in particular, elevated the metabolites of indole-3-acetate, methylsuccinic acid, creatine, glutamic acid, threonine, lysine, ascorbic acid, and pyridoxamine. Spearman's correlation analysis showed the close relation between the different genera and metabolites. In conclusion, Bacillus sp. DU-106 supplement ameliorated high-fat diet-induced hypercholesterolemia and showed potential probiotic benefits for the intestine. Key points: • A novel potential probiotic Bacillus sp. DU-106 ameliorated hypercholesterolemia in rats. • Bacillus sp. DU-106 supplement regulated gut microbiome structure and richness. • Bacillus sp. DU-106 supplement changed metabolic profiles in high-fat diet rats. • Significant correlations were observed between differential genera and metabolites. [ABSTRACT FROM AUTHOR]

Cellulases, as environmentally appropriate catalysts specifically acting on cellulosic substrates, are important for the industrial conversion of lignocellulose and modification of cellulose products. After decades of research, a fundamental understanding of cellulase-mediated hydrolysis of cellulose is that its ability to processively act as a key for the complete enzymatic hydrolysis of natural crystalline cellulose. Two types of processive cellulases are known: exoglucanases and processive endoglucanases. Exoglucanases are typical processive enzymes, and they have been studied in detail so that their modes of action and mechanisms are reasonably well characterized. Conversely, endoglucanases are less well characterized because of the non-universality and structural diversity. However, processive endoglucanases have certain characteristics that exoglucanases lack such as hydrolysis product diversity and independent hydrolyze natural crystalline cellulose. Therefore, besides the conversion of cellulose to monosaccharide, they might be useful for modification of fibrous substrates and preparation of cellulose oligosaccharides. Herein, we review in detail the sources, hydrolysis products, application, and possible hydrolysis mechanisms of processive endoglucanases. [ABSTRACT FROM AUTHOR]

Despite recent advances in the use of porous materials as efficient heterogeneous catalysts which operate through effectively trapping reagents in a well-defined space, continuously uptaking reagents to substitute products in the cavity for efficient product turnover still remains challenging. Here, a porous catalyst is endowed with 'breathing' characteristics by thermal stimulus, which can enable the efficient exchange of reagents and products through reversible stacking from inflated aromatic hexamers to contracted trimeric macrocycles. The contracted super-hydrophobic tubular interior with pyridine environment exhibits catalytic activity towards a nucleophilic aromatic substitution reaction by promoting interactions between concentrated reagents and active sites. Subsequent expansion facilitates the exchange of products and reagents, which ensures the next reaction. The strategy of mesoporous modification with inflatable transition may provide a new insight for construction of dynamic catalysts. Porous materials are efficient heterogeneous catalysts, but the continuous uptake of reagents to substitute products in the cavities remains unsettled. Here the authors fabricate a self-assembled tubular structure with breathing characteristics for efficient exchange of reactants and products in a nucleophilic substitution reaction. [ABSTRACT FROM AUTHOR]

Background: Controversy exists on whether tenofovir disoproxil fumarate (TDF) is superior to entecavir (ETV) in lowering the risk of hepatocellular carcinoma (HCC) development. This meta-analysis was performed to clarify this issue with critical clinical and methodological considerations. Methods: PubMed, EMBASE, and Cochrane Library were searched from inception to Oct 28, 2019. Randomized control trials and observational studies reporting the impact of TDF and ETV on the risk of HCC in patients with chronic hepatitis B (CHB) were eligible. Risk ratios (RRs) calculated with cumulative incidence rate and/or annual incidence rate, or hazard ratio (HR) were pooled using random-effect models. Subgroup analyses were performed to assess the potential impact of between-study level and within-study level factors. Results: A total of 32 studies with 78,136 CHB patients were included. Overall cumulative incidence rate of HCC was lower in TDF group than ETV group (3.07% vs. 5.25%; RR 0.55; 95% CI 0.42–0.72). However, this difference was not statistically significant in pooled results of hazard ratio (HR 0.87; 95% CI 0.73–1.04) and RR calculated with annual incidence rate (RR 0.88; 95% CI 0.67–1.16). Potential confounding factors at between-study level included prior nucleos(t)ide usage, disease stage at baseline and region of study. More importantly, at within-study level, disparity in follow-up duration between TDF and ETV groups may impact the result, usually favoring a treatment with shorter follow-up duration. Conclusions: Compared with ETV, TDF treatment tended to have a lower overall cumulative incidence rate of HCC. However, disparity in follow-up duration may be a key factor to influence the result. [ABSTRACT FROM AUTHOR]

Cylindrical luffa has potential to be a lightweight mattress cushioning material with good air permeability, dryness and comfort. However, it is extremely firm and requires suitable softening treatment prior to use. In this work, the effects of three alkali-based softening treatments on the chemical composition, microstructure, physical and mechanical properties, and water absorption and desorption properties of high-density (HD) luffa fiber bundles were investigated. The softening treatment with 5% NaOH/5% H2O2 significantly lowered the compressive strength and plateau stress of HD cylindrical luffa by 77% and 73%, respectively. Moreover, large amounts of lignin, hemicellulose and amorphous cellulose were removed from HD luffa fibers after the treatment, resulting in loosening of the HD luffa fiber cells and fiber bundles. Although the softening treatment with 10% NaOH/20% CH3COOH only slightly reduced the compressive strength and plateau stress of HD cylindrical luffa, it significantly improved the flexibility of HD luffa fiber bundles. After being separately treated by 5% NaOH/5% H2O2, 10% NaOH/20% CH3COOH, and 18% NaOH/1.6% CO(NH2)2, the water desorption ratios of HD luffa after 12 h were all increased and reached 94%, 90% and 93%, respectively. The results indicated that the softening treatment with 10% NaOH/20% CH3COOH was a suitable method for obtaining softer and durable HD cylindrical luffa as potential mattress cushioning material. The schematic diagram of three softening treatments. (a) Hierarchical structures of the luffa cylinders, (b) and (c) changes in the microfibril structure before and after HD luffa cylinders were treated by Methods 1, 2, and 3. [ABSTRACT FROM AUTHOR]

A dual-receptor targeting delivery system based on acid-cleavage hydrazone bond was developed in the study. The characters of CMCS-hyd-CUR-EGFR- mAb were identifed. The in vitro release studies revealed that this drug delivery system was acid-sensitive, and the self-assembled nanoparticles which were spherical. The in vitro results indicated that the dual-receptor targeting nanoparticles could be faster internalized into the Cal-27 cells via receptor-mediated endocytosis, which exhibited better antitumor activity than the one-receptor nanoparticles. The experimental results clearly reveal that CMCS-hyd-CUR-EGFR mAb provides a novel way for drug delivery in oral cancer treatment. [ABSTRACT FROM AUTHOR]

The Linfen rift is a Cenozoic extensional rift with significant seismicity and seismic hazards. Studies of this rift shed light on deep dynamic processes and seismogenic mechanisms relevant to crustal structure and seismic activity. We first conducted a joint inversion of receiver functions and surface wave dispersion on waveform data collected from 27 broadband seismic stations to image the crustal S-wave velocity in the Linfen rift and its surroundings. We then relocated the source parameters for 10 earthquake events with depths>20 km and studied the relationship between crustal S-wave velocity and seismicity. The results show that low-velocity zones of different scales exist in the middle-lower crust, and that the depth of the seismogenic layer gradually increases from ~25 km in the south to ~34 km in the north, roughly corresponding to the bottom of the low-velocity zone.We found that most of the relocated earthquakes occurred in the low-velocity zone at depths of 18 km to 34 km, with the deepest at 32 km. Two of the greatest historic earthquakes, Linfen (Ms 7.75) in 1695 and Hongtong (Ms 8.0) in 1303, occurred at the bottom of the high-velocity zone at depths of 12 km to 18 km. Our results, combined with previous studies, suggest that the upwelling mantle material below the rift did not remarkably affect the velocity structure from the bottom of the seismogenic layer down to the uppermost mantle nor heat the crust. It is likely that neither crustal-scale faults nor mantle earthquakes exist in the Linfen rift. [ABSTRACT FROM AUTHOR]

Background and aims: Non-alcoholic fatty liver disease (NAFLD) commonly affects subjects with obesity, yet non-obese NAFLD is increasingly being recognized. We aimed to investigate the clinicopathological and genetic characteristics of non-obese NAFLD patients. Methods: The clinical, histological and genetic data of 84 NAFLD patients with biopsy for abnormal liver function test were reviewed. Both NAS-CRN and SAF scoring systems were applied for histopathological evaluation. PNPLA3 and TMS6F2 genotyping were also performed. Results: All of the 84 patients were histologically diagnosed with non-alcoholic steatohepatitis (NASH), with 36 of them (42.9%) being non-obese (BMI < 25 kg/m2). Compared with the obese group, non-obese group were predominantly females (88.9% vs 52.1%, p < 0.001), tended to have higher prevalence of diabetes (p = 0.068). More importantly non-obese patients had a significant higher prevalence of advanced fibrosis (F ≥ 3) (58.3% vs 29.2%, p = 0.013), and a trend of higher degree of ballooning (p = 0.061). In addition, values of liver stiffness measurement were also significantly higher in non-obese group (12.1 kPa vs 8.1 kPa, p = 0.032). There was also a trend of higher prevalence of TM6SF2 T allele in non-obese group (p = 0.085), while the prevalence of PNPLA3 risk allele did not differ between two groups. Multivariate analysis showed that higher fasting glucose (p = 0.038) and lower serum platelets (p = 0.040) were two independent predictors for advanced fibrosis in non-obese patients. Conclusions: Non-obese NASH patients have a female predominance and more advanced fibrosis. Liver biopsy is crucial to evaluate the severity of disease in non-obese patients especially those with abnormal liver biochemistry. Clinical trial number: NCT03386890. [ABSTRACT FROM AUTHOR]

Aims: Epidemiological studies on primary biliary cholangitis (PBC) show heterogeneity. The aim of the present study was to synthesize the prevalence, incidence and clinical course of PBC in the Asia–Pacific region. Methods: PubMed, Medline, Cochrane library and EMBASE were searched for epidemiology and clinical course of PBC published up to July, 2019. Meta-analysis was conducted on the epidemiology and clinical course (decompensation, hepatocellular carcinoma and death/liver transplantation) of PBC patients. Random-effect model and fixed-effect model were used to evaluate the pooled prevalence, incidence, mortality/liver transplantation and their 95% confidence intervals as appropriate. Subgroup analysis was performed by stratification with gender, pre- and post-UDCA era, sub-region and publication year. Meta-regression was used to examine the heterogeneity. Results: Out of 3460 studies, 18 studies from 7 countries/regions were finally included. The overall prevalence of PBC was 118.75 cases per million (95% CI 49.96–187.55) in the Asia–Pacific region, with the high, medium and low prevalence being in Japan and China (191.18 cases per million), New Zealand (99.16 cases per million) and South Korea and Australia (39.09 cases per million), respectively. The incidence of PBC was 8.55 cases per million per year (95% CI 8.05–9.06). The 5-year accumulative incidence of decompensation, HCC and death/liver transplantation in PBC patients was 6.95% (95% CI 2.07–11.83%), 1.54% (95% CI 0.9–2.19%) and 4.02% (95% CI 2.49–5.54%), respectively. Conclusion: In the Asia–Pacific region, the prevalence and incidence of PBC are higher than once expected. PBC tends to be diagnosed at older age and has a relatively low incidence of HCC in this region. [ABSTRACT FROM AUTHOR]

Objective and design: The present study aimed to investigate the relationship between the disturbed balance of CD4+/CD8+, Th17/Treg and the activation of the Notch signaling pathway in experimental autoimmune uveitis (EAU). Methods: An EAU rat model was induced in Lewis rats, and pathology analysis was performed by hematoxylin and eosin (H&E) staining. CD4+, CD8+, Th17, and Treg levels in spleen, lymph nodes and eye tissues were determined by flow cytometry. Meanwhile, the expression of Notch1, DLL4, IL-10, and IL-17 was determined by quantitative polymerase chain reaction (Q-PCR) and enzyme-linked immunosorbent assay (ELISA). In addition, the inhibitory effect of N-(N-(3,5-difluorophenacetyl-l-alanyl))-S-phenylglycine t-butyl ester (DAPT) on Th17 differentiation by Notch signaling in vitro was further investigated using T lymphocytes from EAU rats on day 12 post-immunization by flow cytometry. Results: The pathological results showed that inflammatory cell infiltration occurred in ocular tissues in EAU rats. The CD4+/CD8+ and Th17/Treg ratios in EAU rats were apparently higher than those in normal control individuals. Q-PCR and ELISA analyses indicated the expression of Notch1, DLL4, IL-10, and IL-17 in EAU rats gradually increased on day 6 after immunization, peaked on day 12, and then gradually decreased. The dynamic trends in Notch1 and DLL4 expression in EAU rats were identical to those of CD4+/CD8+ and Th17/Treg levels. DAPT can significantly inhibit the activation of Notch signaling, decrease Th17 cell differentiation, and attenuate the level of the Th17 cell lineage, contributing to the balance of the Th17/Treg ratio. Conclusion: The activation of the Notch signaling pathway can regulate Th17 and Treg cell differentiation, disrupt the CD4+/CD8+ and Th17/Treg balance, and aggravate the severity of EAU; inactivation of the Notch signaling pathway contributes to the CD4+/CD8+ and Th17/Treg balance in EAU rats. Our findings highlighted that the dynamic change in the CD4+/CD8+ and Th17/Treg ratio was consistent with the expression trend of Notch signaling in EAU rats, suggesting that Notch signaling may be a potentially important therapeutic target in clinical practice. [ABSTRACT FROM AUTHOR]

Background and aims: Sampling size variability of liver biopsy remains a major limitation in the assessment of liver fibrosis. We aimed to evaluate the diagnostic value of a fully quantitative method (second harmonic generation/two-photon excitation fluorescence, SHG/TPEF based) in "short" liver biopsy samples. Methods: Liver biopsy samples from chronic hepatitis B (CHB) patients were constructed into "virtual" biopsies with different lengths. The original and "virtual" samples were measured by SHG/TPEF-based technology to obtain qFibrosis score, respectively. Here, ΔqFibrosis was defined as difference of qFibrosis between original biopsy and "virtual" biopsy. Equivalence test was used to compare ΔqFibrosis with the clinically acceptable error (deviation of 0.50) in each group. Results: In real-world practice, qFibrosis score increased significantly with fibrosis progression in ≥ 1.5-cm-, 1.0–1.5-cm-, and 0.5–1.0-cm-long specimens (p < 0.05), compared with ≤ 0.5-cm-long specimens (p > 0.05). In virtual biopsy samples with specified length, the equivalence was confirmed in 0.5–1.0-cm- and 1.0–1.5-cm-long specimens (0.27 vs. 0.22, p < 0.001), whereas not in ≤ 0.5-cm-long specimens (0.53, p > 0.05). The number of cross-linked collagen fibers, the total and aggregated collagen proportionate area, and the collagen strings in number, length, width and perimeter showed excellent consistency with original biopsy samples in 0.5–1.0-cm- and 1.0–1.5-cm-long specimens (ICC > 0.90). Conclusions: The use of SHG/TPEF-based image technology may give useful suggestive information in evaluation of CHB-related liver fibrosis for the short sample (biopsy length > 0.5 cm). [ABSTRACT FROM AUTHOR]

Background and aims: Non-invasive fibrosis assessment has been highly recommended in many liver diseases. However, comparative diagnostic accuracy of laboratory markers, ultrasound and magnetic resonance elastography (MRE) for fibrosis in autoimmune hepatitis (AIH) patients has not been established.Methods: Medline, Embase and Cochrane Library were searched. Primary outcome was significant fibrosis (SF), advanced fibrosis (AF) and cirrhosis, defined as Metavir stage F ≥ 2, F ≥ 3 and F = 4 according to liver biopsy. Hierarchical summary receiver operating characteristic curve (ROC) model was used to evaluate diagnostic accuracy of non-invasive methods. Summary area under ROC (AUROC) and diagnostic odds ratio (DOR) with 95% confidence interval (CI) were calculated. The Grading of Recommendations Assessment, Development and Evaluation system was used to assess quality of evidence.Results: Overall, 16 studies with 861 patients were included, comparing aspartate aminotransferase to platelet ratio index (APRI), fibrosis-4 index (FIB-4), aspartate aminotransferase/alanine aminotransferase ratio, transient elastography (TE), acoustic radiation force impulse, shear wave elastography and MRE versus liver biopsy. Among all non-invasive markers, TE had good performance for fibrosis staging. Summary AUROCs and DORs of TE were 0.90 (95% CI 0.87, 0.92) and 23.7, 0.91 (95% CI 0.89, 0.93) and 31.6, 0.89 (95% CI 0.86, 0.92) and 80.5 for staging SF, AF and cirrhosis, whereas APRI and FIB-4 showed poor performance for detecting AF (DOR, 4.6 and 4.7) and cirrhosis (DOR, 5.5 and 12.9).Conclusions: TE performs well to stage liver fibrosis in patients with AIH, compared with other laboratory non-invasive indexes. Nevertheless, diagnostic accuracy of APRI and FIB-4 is poor. [ABSTRACT FROM AUTHOR]