Unravelling the Impact of RNA Methylation Genetic and Epigenetic Machinery in the Treatment of Cardiomyopathy.

Cardiomyopathy (CM) represents a heterogeneous group of diseases primarily affecting cardiac structure and function, with genetic and epigenetic dysregulation playing a pivotal role in its pathogenesis. Emerging evidence from the burgeoning field of epitranscriptomics has brought to light the significant impact of various RNA modifications, notably N6-methyladenosine (m6A), 5-methylcytosine (m5C), N7-methylguanosine (m7G), N1-methyladenosine (m1A), 2'-O-methylation (Nm), and 6,2'-O-dimethyladenosine (m6Am), on cardiomyocyte function and the broader processes of cardiac and vascular remodelling. These modifications have been shown to influence key pathological mechanisms including mitochondrial dysfunction, oxidative stress, cardiomyocyte apoptosis, inflammation, immune response, and myocardial fibrosis. Importantly, aberrations in the RNA methylation machinery have been observed in human CM cases and animal models, highlighting the critical role of RNA methylating enzymes and their potential as therapeutic targets or biomarkers for CM. This review underscores the necessity for a deeper understanding of RNA methylation processes in the context of CM, to illuminate novel therapeutic avenues and diagnostic tools, thereby addressing a significant gap in the current management strategies for this complex disease.

Induced domestication of humic reduction-denitrification coupled bacteria improved treatment of sediment: Performance, remediation effect, and metabolic mechanisms.

The high organic matter in river sediment primarily induces black and odorous rebound. Traditional humic-reducing bacteria demonstrate relatively single metabolic functions and restrain the remediation within complex sediment environments. In addition, Ca(NO3)2 is commonly utilized in synergistic with bioremediation to improve the reducing environment of sediments. In this study, a multifunctional bacterial community with humic reduction-denitrification coupled bacteria was domesticated by the step-feeding strategy in an anaerobic baffle reactor (ABR). The performance, remediation effect, and metabolic mechanisms were analyzed. The results indicated that humic-reducing bacteria (HRB) and denitrifying-humic-reducing bacteria (DF/HRB) have quinone-reduction and denitrification capabilities. The synergistic effect of DF/HRBs and Ca(NO3)2 was superior to HRBs and Ca(NO3)2 on the removal of total organic matter(TOM). Microbial community structure analysis revealed an enhanced relative abundance of denitrification and humic-reducing bacteria (e.g., Thauera, Pseudomonas, Sulfurospirillum, Desulfovibrio, Geobacter) in the DF/HRB, resulting in a superior synergistic effect of DF/HRBs with Ca(NO3)2. This work helps to present an innovative approach to domesticate humic-reducing bacteria suited for the remediation environment effectively. It also expands the application of humic-reducing bacteria for in-situ anaerobic remediation of river sediments.

Time Convolutional Network-Based Maneuvering Target Tracking with Azimuth-Doppler Measurement.

In the field of maneuvering target tracking, the combined observations of azimuth and Doppler may cause weak observation or non-observation in the application of traditional target-tracking algorithms. Additionally, traditional target tracking algorithms require pre-defined multiple mathematical models to accurately capture the complex motion states of targets, while model mismatch and unavoidable measurement noise lead to significant errors in target state prediction. To address those above challenges, in recent years, the target tracking algorithms based on neural networks, such as recurrent neural networks (RNNs), long short-term memory (LSTM) networks, and transformer architectures, have been widely used for their unique advantages to achieve accurate predictions. To better model the nonlinear relationship between the observation time series and the target state time series, as well as the contextual relationship among time series points, we present a deep learning algorithm called recursive downsample-convolve-interact neural network (RDCINN) based on convolutional neural network (CNN) that downsamples time series into subsequences and extracts multi-resolution features to enable the modeling of complex relationships between time series, which overcomes the shortcomings of traditional target tracking algorithms in using observation information inefficiently due to weak observation or non-observation. The experimental results show that our algorithm outperforms other existing algorithms in the scenario of strong maneuvering target tracking with the combined observations of azimuth and Doppler.

[Tetramethylpyrazine regulates angiogenesis of endothelial cells in cerebral ischemic stroke injury via SIRT1/VEGFA signaling pathway].

This study aims to investigate whether tetramethylpyrazine(TMP) can stimulate angiogenesis in cerebral microvascular endothelial cells and alleviate cerebral ischemic stroke(CIS) and to explore the underlying mechanisms. In the animal study, adult Sprague-Dawley rats(n=15) were assigned into sham surgery(sham), middle cerebral artery occlusion/reperfusion(MCAO/R), and MCAO/R+TMP(intraperitoneal injection of 20 mg·kg~(-1)) groups. The neurological function was evaluated by the Z-Longa method. The cerebral infarction volume was detected by TTC staining. Enzyme-linked immunosorbent assay(ELISA) was employed to detect the expression of vascular endothelial growth factor(VEGF), angiopoietin(Ang), and platelet-derived growth factor(PDGF). Immunofluorescence staining was employed to detect Ki67 and the expression of vascular endothelial growth factor A(VEGFA) and slient information regulator 1(SIRT1). Western blot was employed to determine the expression levels of VEGFA, SIRT1, angiopoietin-2(Ang-2), and platelet-derived growth factor B(PDGFB). In the cell study, mouse brain-derived endothelial cells(Bend.3) were cultured, and the optimal concentration of TMP was determined. Then, VEGF, Ang, and PDGF were detected by ELISA after the addition of cabozantinib. Western blot was employed to measure the expression of VEGFA, Ang-2, and PDGFB. Immunofluorescence staining was used to detect CD31, CD34, and Ki67, and the proliferation, migration, and tube formation ability of Bend.3 cells were observed in vitro. Western blot and immunofluorescence staining were performed to measure the expression of SIRT1 and VEGFA after addition of the SIRT1-specific inhibitor selisistat(EX-527). The results showed that compared with the sham group, the MCAO/R group had severe neurological function damage, increased infarction volume, up-regulated expression of VEGF, VEGFA, Ang, Ang-2, PDGF, and PDGFB, and down-regulated expression of Ki67 and SIRT1(P<0.01). Compared with the MCAO/R group, the MCAO/R+TMP group presented alleviated neurological function damage, reduced infarction volume, and activated expression of VEGF, VEGFA, Ang, Ang-2, PDGF, PDGFB, Ki67, and SIRT1(P<0.01). The cell experiments showed that compared with the normal group, Bend.3 cells were activated by oxygen glucose deprivation/reoxygenation(OGD/R) treatment(P<0.05, P<0.01). Compared with the OGD/R group, the OGD/R+TMP group upregulated the expression levels of VEGF, VEGFA, Ang, Ang-2, PDGF, PDGFB, SIRT1, Ki67, CD31, and CD34, enhanced the angiogenic ability of Bend.3 cells without being inhibited by BMS or EX-527(P<0.05, P<0.01, P<0.001). The results suggest that TMP can activate the SIRT1/VEGFA signaling pathway to stimulate angiogenesis and alleviate CIS injury.

Endothelial progenitor cell-derived exosomes promote anti-inflammatory macrophages via SOCS3/JAK2/STAT3 axis and improve the outcome of spinal cord injury.

BACKGROUND: Macrophage in the spinal cord injury (SCI) area imparts a chronic pro-inflammation effect that challenges the recovery of SCI. Previously, endothelial progenitor cell-produced exosomes (EPC-EXOs) have been noticed to facilitate revascularization and inflammation control after SCI. However, their effects on macrophage polarization remained unclear. This study aimed to investigate the EPC-EXOs' role in macrophage polarization and reveal its underlying mechanism. METHODS: We extracted the macrophages and EPC from the bone marrow suspension of C57BL/L mice by centrifugation. After cell identification, the EPC-EXOs were collected by ultra-high-speed centrifugation and exosome extraction kits and identified by transmission electron microscopy and nanoparticle tracking analysis. Then, macrophages were cultured with EPC-EXOs in different concentrations. We labeled the exosome to confirm its internalization by macrophage and detected the macrophage polarization marker level both in vitro and in vivo. We further estimated EPC-EXOs' protective effects on SCI by mice spinal cord tissue H&E staining and motor behavior evaluation. Finally, we performed RT-qPCR to identify the upregulated miRNA in EPC-EXOs and manipulate its expression to estimate its role in macrophage polarization, SOCS3/JAK2/STAT3 pathway activation, and motor behavior improvement. RESULTS: We found that EPC-EXOs decreased the macrophages' pro-inflammatory marker expression and increased their anti-inflammatory marker expression on the 7 and 14 days after SCI. The spinal cord H&E staining results showed that EPC-EXOs raised the tissue-sparing area rate significantly after 28 days of SCI and the motor behavior evaluation indicated an increased BMS score and motor-evoked potential by EPC-EXOs treatment after SCI. The RT-qPCR assay identified that miR-222-3P upregulated in EPC-EXOs and its miRNA-mimic also decreased the pro-inflammatory macrophages and increased the anti-inflammatory macrophages. Additionally, miR-222-3P mimic activated the SOCS3/JAK2/STAT3 pathway, and SOCS3/JAK2/STAT3 pathway inhibition blocked miR-2223P's effects on macrophage polarization and mouse motor behavior. CONCLUSION: Comprehensively, we discovered that EPC-EXOs-derived miR-222-3p affected macrophage polarization via SOCS3/JAK2/STAT3 pathway and promoted mouse functional repair after SCI, which reveals EPC-EXOs' role in modulation of macrophage phenotype and will provide a novel interventional strategy to induce post-SCI recovery.

Chen's penetrating-suture technique for pancreaticojejunostomy following pancreaticoduodenectomy.

BACKGROUND: Postoperative pancreatic fistula (POPF) is the most serious complication and the main reason for morbidity and mortality after pancreaticoduodenectomy (PD). Currently, there exists no flawless pancreaticojejunal anastomosis approach. We presents a new approach called Chen's penetrating-suture technique for pancreaticojejunostomy (PPJ), which involves end-to-side pancreaticojejunostomy by suture penetrating the full-thickness of the pancreas and jejunum, and evaluates its safety and efficacy. METHODS: To assess this new approach, between May 2006 and July 2018, 193 consecutive patients who accepted the new Chen's Penetrating-Suture technique after a PD were enrolled in this study. Postoperative morbidity and mortality were evaluated. RESULTS: All cases recovered well after PD. The median operative time was 256 (range 208-352) min, with a median time of 12 (range 8-25) min for performing pancreaticojejunostomy. Postoperative morbidity was 19.7% (38/193) and mortality was zero. The POPF rate was 4.7% (9/193) for Grade A, 1.0% (2/193) for Grade B, and no Grade C cases and one urinary tract infection. CONCLUSION: PPJ is a simple, safe, and reliable technique with ideal postoperative clinical results.

The mechanism of C-N-S interconnection degradation in organic-rich sediments by Ca(NO3)2 - CaO2 synergistic remediation.

The rebound of black-odorous occurred in organic-rich sediments has become a critical issue due to its great harm to the ecological environment. Elements such as S, C, and N play a crucial role in the biogeochemical cycle of black-odorous rivers. As electronic acceptors, Ca(NO3)2 and CaO2 can effectively remove acidified volatile sulfide (AVS) and organic matter to control the black-odorous rebound. However, the remediation mechanisms in organic-rich sediments by Ca(NO3)2 and CaO2 are unclear. The present study explored the mechanism of C-N-S interconnection degradation in organic-rich urban river sediments by adding different ratios and sequences of Ca(NO3)2 and CaO2. The results showed that Ca(NO3)2 remediation followed by CaO2 and the accepted electron ratio 1:1 of Ca(NO3)2 to CaO2 is an effective method for controlling the rebound of black-odorous and reducing the accumulation NO2--N. Mainly attributed to that, CaO2 enhanced the degradation of organic matter by stimulating enzymatic activities in the sediments, which is also the main reason for controlling the rebound of black-odorous. Since CaO2 releases O2 and •OH, which inhibit nosZgenes, NO2--N accumulates when remedied simultaneously with Ca(NO3)2 and CaO2. Co-occurrence network analysis illustrated that sulfur-driven autotrophic denitrification bacteria, heterotrophic denitrifying bacteria, and sulfate-reducing bacteria interact strongly inside one module, clarifying a solid interaction of C-N-S substances among these bacteria. Our results reveal the C-N-S interconnection degradation mechanism and provide a new perspective on applying biochemical remediation in organic-rich urban river sediments.

Association of BIRC5 Gene Polymorphism with the Collateral Circulation and Severity of Large Artery Atherosclerotic Stroke.

Objectives: The collateral circulation near the cerebral artery occlusion can contribute to the relief of the symptoms and signs of stroke. Genetic factors play a decisive role in the difference in collateral circulation. Survivin, encoded by the baculoviral inhibitor of apoptosis (IAP) repeat-containing 5 gene (BIRC5), plays an important role in maintaining long-term endothelial integrity and homeostasis and as an angiogenic factor in the treatment of vascular diseases. We hypothesized that genetic variations in the BIRC5 gene may contribute to severity by influencing the collateral circulation. This study aimed at examining how the polymorphism of the BIRC5 gene correlated with the collateral circulation and severity of large artery atherosclerotic stroke. Methods: This study enrolled 428 patients with large artery atherosclerotic stroke. There are no statistical differences in age, sex, social behavior, such as smoking and drinking, between the groups classified by the collateral circulation and by the severity of stroke (P > 0.01). Direct sequencing was performed for the genotyping of single nucleotide polymorphism (SNP) of BIRC5 (rs2071214). The enrolled patients were divided into several subgroups based on the collateral flow grading system from the American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology (ASITN/SIR), the results of the National Institutes of Health Stroke Survey (NIHSS) (6 as a threshold), and the score of the modified Rankin scale (mRS) (for the prediction of prognosis, 2 as a threshold). Differences among subgroups were identified through logistic regression. Results: The analysis of collateral circulation revealed the significant correlation of SNP of rs2071214 with the development of poor collateral circulation of large artery atherosclerotic stroke in the additive model (GG vs. AA, odds ratio (OR) = 3.592, 95% confidence interval (CI) = 1.410-9.150, and P=0.007) and the recessive model (GG vs. AA/GA, OR = 3.313, 95% CI = 1.420-7.727, and P=0.006). The analysis of stroke severity exposed the significant role of the SNP of rs2071214 in increasing stroke severity in the dominant model (GA/GG vs. AA, OR = 1.658, 95% CI = 1.017-2.703, and P=0.043) and the additive model (GA vs. AA, OR = 1.717, 95% CI = 1.021-2.888, and P=0.042). However, the analysis of the short-term outcome indicated that three genetic models were not associated with short-term outcomes in the additive model (GA vs. AA, P=0.815, GG vs. AA, and P=0.336), the dominant model (GA/GG vs. AA and P=0.589), and the recessive model (GG vs. AA/GA and P=0.342). Conclusion: Our findings identified the SNP of rs2071214 of the BIRC5 gene as a risk factor for the poor compensatory ability of collateral circulation and a predictor of stroke severity in large artery atherosclerotic stroke, which suggested that the SNP of rs2071214 can serve as an innovative therapeutic target for patients with acute ischemic stroke.

Deep Learning Approach to UAV Detection and Classification by Using Compressively Sensed RF Signal.

Recently, the frequent occurrence of the misuse and intrusion of UAVs has made it a research challenge to identify and detect them effectively, and relatively high bandwidth and pressure on data transmission and real-time processing exist when sampling UAV communication signals using the RF detection method. In this paper, firstly, for data sampling, we chose a compressed sensing technique to replace the traditional sampling theorem and used a multi-channel random demodulator to sample the signal; secondly, for the detection and identification of the presence, type, and flight pattern of UAVs, a multi-stage deep learning-based UAV identification and detection method was proposed by exploiting the difference in communication signals between UAVs and controllers under different circumstances. The data samples are first passed by detectors that detect the presence of UAVs, then classifiers are used to identify the type of UAVs, and finally flight patterns are judged by the corresponding classifiers, for which two neural network structures (DNN and CNN) are constructed by deep learning algorithms and evaluated and validated by a 10-fold cross-validation method, with the DNN network used for detectors and the CNN network for subsequent type and flying mode classification. The experimental results demonstrate, first, the effectiveness of using compressed sensing for sampling the communication signals of UAVs and controllers; and second, the detecting method with multi-stage DL detects higher efficiency and accuracy compared with existing detecting methods, detecting the presence, type, and flight model of UAVs with an accuracy of over 99%.

Modelling the effects of Wuhan's lockdown during COVID-19, China.

OBJECTIVE: To design a simple model to assess the effectiveness of measures to prevent the spread of coronavirus disease 2019 (COVID-19) to different regions of mainland China. METHODS: We extracted data on population movements from an internet company data set and the numbers of confirmed cases of COVID-19 from government sources. On 23 January 2020 all travel in and out of the city of Wuhan was prohibited to control the spread of the disease. We modelled two key factors affecting the cumulative number of COVID-19 cases in regions outside Wuhan by 1 March 2020: (i) the total the number of people leaving Wuhan during 20-26 January 2020; and (ii) the number of seed cases from Wuhan before 19 January 2020, represented by the cumulative number of confirmed cases on 29 January 2020. We constructed a regression model to predict the cumulative number of cases in non-Wuhan regions in three assumed epidemic control scenarios. FINDINGS: Delaying the start date of control measures by only 3 days would have increased the estimated 30 699 confirmed cases of COVID-19 by 1 March 2020 in regions outside Wuhan by 34.6% (to 41 330 people). Advancing controls by 3 days would reduce infections by 30.8% (to 21 235 people) with basic control measures or 48.6% (to 15 796 people) with strict control measures. Based on standard residual values from the model, we were able to rank regions which were most effective in controlling the epidemic. CONCLUSION: The control measures in Wuhan combined with nationwide traffic restrictions and self-isolation reduced the ongoing spread of COVID-19 across China.

Removal of lead from two polluted soils by magnetic wheat straw biochars.

Due to high sorption capacity for heavy metals, magnetic biochar (MBC) has the potential to adsorb heavy metals in soils, which are then removed together with MBC from soils by a magnetic field. In this study, two magnetic biochars (MBC300 and MBC700) were derived from the magnetization of wheat straw biochars pyrolyzed at 300 and 700 °C. Strong binding of Pb with iron oxide particles deposited on biochar was observed. After the MBCs (7.5%, w/w) were applied to two naturally Pb-polluted soils (named as He-soil and Hu-soil) for 720 h, the removal efficiency of Pb from the soil by MBC300 (26.8-40.1%) was similar (p > 0.05) to that by MBC700 (25.1-42.1%). This is because MBC300 has lower sorption capacity for Pb but higher recovery percentage from soils as a result of lower saturation magnetization. The removal efficiencies of Pb by the two MBCs were 13-17% higher for He-soil than for Hu-soil, which was due to higher proportion of mobile forms of Pb in He-soil (82.3%) than in Hu-soil (51.5%). Spectroscopic analysis indicated that Pb in soils tended to bind onto the surface of MBC in more stable forms. Moreover, removing Pb from soils by MBC could decrease Pb concentration in ryegrass by about 30%. Therefore, it might be a potential method to remedy Pb-polluted soils.

miR-148-3p and miR-152-3p synergistically regulate prostate cancer progression via repressing KLF4.

BACKGROUND: miR-148-3p and miR-152-3p as the tumor suppressors have been reported in various cancer types. Our study is aimed to discuss the synergistic effect of miR-148-3p and miR-152-3p in prostate cancer (PCa). METHODS: Bioinformatics algorithm and luciferase reporter assays were used to verify whether miR-148-3p and 152-3p could bind with the 3'-untranslated region (3'-UTR) of Kruppel-like factor 4 (KLF4). PCa cell growth in vivo was analyzed using the mouse xenograft tumor model. RESULTS: miR-148-3p and miR-152-3p were reduced in PCa tumor tissues. Moreover, the protein expression of KLF4 was increased in PCa tissues. The 3'-UTR of KLF4 contained the conserved binding sites with miR-148-3p and miR-152-3p. The mimics or inhibitors of miR-148-3p and/or miR-152-3p could downregulated or upregulated KLF4 expression, respectively. miR-148-3p and miR-152-3p-induced PCa cell growth inhibition were observed both in vivo and in vitro. KLF4 overexpression had the ability to neutralize the antitumor effect of miR-148-3p/152-3p in vivo and in vitro. CONCLUSION: miR-148-3p/152-3p family could serve as tumor suppressors in PCa via repressing KLF4.

Additive interaction of snoring and body mass index on the prevalence of metabolic syndrome among Chinese coal mine employees: a cross-sectional study.

BACKGROUND: Although snoring has been previously reported to be associated with metabolic syndrome (MetS), its interaction with body mass index(BMI) on MetS remains unclear. We aimed to examine the individual effects and possible interaction between snoring and BMI on MetS. METHODS: From July 2013 to December 2013, 3794 employees of coal mining enterprises aged 18 to 65 were recruited from Shanxi province of China. The individual effects were assessed by multivariable logistic regression model. Additive interaction was evaluated by calculating the relative excess risk due to interaction (RERI), attributable proportion due to interaction (AP) and synergy index(S). RESULTS: We found that, after adjusting for potential confounders, odds ratio (OR) and 95% CI for MetS was 1.30 (1.09, 1.56) in occasional snorers and 1.50 (1.24, 1.82) in habitual snorers compared with non-snorers. BMI ≥ 24 was related to high risk of MetS (OR, 3.27; 95% CI, 2.93-3.63). Significant additive interaction between snoring and BMI on MetS was detected. The estimates and 95% CI of the RERI, AP and S were 1.89 (0.67, 3.24), 0.23 (0.08, 0.38), and 1.37 (1.11, 1.75), respectively. However, stratified by workplace, the additive interaction was only significant among underground front-line and ground workers. CONCLUSIONS: Both Snoring and BMI were related to high risk of Mets. Moreover, there are additive interaction between snoring and BMI. Snorers who worked underground front-line and ground are more susceptible to the negative impact of being overweight on MetS.

A novel fluorescent biosensor based on dendritic DNA nanostructure in combination with ligase reaction for ultrasensitive detection of DNA methylation.

BACKGROUND: DNA methylation detection is indispensable for the diagnosis and prognosis of various diseases including malignancies. Hence, it is crucial to develop a simple, sensitive, and specific detection strategy. METHODS: A novel fluorescent biosensor was developed based on a simple dual signal amplification strategy using functional dendritic DNA nanostructure and signal-enriching polystyrene microbeads in combination with ligase detection reaction (LDR). Dendritic DNA self-assembled from Y-DNA and X-DNA through enzyme-free DNA catalysis of a hairpin structure, which was prevented from unwinding at high temperature by adding psoralen. Then dendritic DNA polymer labeled with fluorescent dye Cy5 was ligated with reporter probe into a conjugate. Avidin-labeled polystyrene microbeads were specifically bound to biotin-labeled capture probe, and hybridized with target sequence and dendritic DNA. LDR was triggered by adding Taq ligase. When methylated cytosine existed, the capture probe and reporter probe labeled with fluorescent dye perfectly matched the target sequence, forming a stable duplex to generate a fluorescence signal. However, after bisulfite treatment, unmethylated cytosine was converted into uracil, resulting in a single base mismatch. No fluorescence signal was detected due to the absence of duplex. RESULTS: The obtained dendritic DNA polymer had a large volume. This method was time-saving and low-cost. Under the optimal experimental conditions using avidin-labeled polystyrene microbeads, the fluorescence signal was amplified more obviously, and DNA methylation was quantified ultrasensitively and selectively. The detection range of this sensor was 10-15 to 10-7 M, and the limit of detection reached as low as 0.4 fM. The constructed biosensor was also successfully used to analyze actual samples. CONCLUSION: This strategy has ultrasensitivity and high specificity for DNA methylation quantification, without requiring complex processes such as PCR and enzymatic digestion, which is thus of great value in tumor diagnosis and biomedical research.

Early Serum HBsAg Drop Is a Strong Predictor of HBeAg Seroconversion and HBsAg Loss to Pegylated Interferon Alfa-2a in Chronic Hepatitis B Patients with Prior Nucleos(t)ide Analogue Exposure.

BACKGROUND High rates of HBeAg and/or HBsAg seroconversion or clearance have been achieved in chronic hepatitis B (CHB) patients receiving pegylated interferon (pegIFN) in addition to ongoing nucleos(t)ide analogue (NUC) treatment. In the present study, we aimed to evaluate HBsAg kinetics to predict HBeAg seroconversion and HBsAg clearance in these patients. MATERIAL AND METHODS A total of 33 HBeAg-positive and 17 HBeAg-negative patients were enrolled between January 2010 and January 2018. At the end of pegIFN treatment, 9 of 50 patients achieved HBsAg clearance, and 9 of 33 HBeAg-positive patients achieved HBeAg seroconversion. RESULTS The cutoff value of 0.41 log10 IU/mL in HBsAg decline at week 12 had a positive predictive value (PPV) of 58.3% and a negative predictive value (NPV) of 94.6% for HBsAg clearance. The cutoff value of 1.94 log10 IU/mL in HBsAg decline at week 24 had a PPV of 80.0% and an NPV of 97.5% for HBsAg clearance. The cutoff value of 0.47 log10 IU/mL in HBsAg decline at week 12 had a PPV of 83.3% and an NPV of 85.2% for HBeAg seroconversion. The cutoff value of 1.29 log10 IU/mL in in HBsAg decline at week 24 had a PPV of 85.7% and an NPV of 88.5% for HBeAg seroconversion. CONCLUSIONS Early HBsAg drop has a high predictive value for HBsAg clearance and HBeAg seroconversion in patients who were treated with combination therapy of pegIFN and NUCs.

Associations between dietary patterns and 10-year cardiovascular disease risk score levels among Chinese coal miners--a cross-sectional study.

BACKGROUND: Diet-related cardiovascular diseases have produced a large health burden in China. Coal miners are a high-risk population for cardiovascular disease, but there is little evidence concerning associations between coal miners' dietary patterns and their 10-year cardiovascular disease risk score levels. METHODS: The study included 2632 participants and focused on dietary patterns associated with higher 10-year cardiovascular disease risk score levels. A valid semi-quantitative food frequency questionnaire was used to collect data regarding dietary intake, and dietary patterns were identified using factor analysis combined with cluster analysis. Logistic regression was used to assess associations between dietary patterns and 10-year cardiovascular disease risk score levels. RESULTS: For ground workers, compared with the 'Healthy' pattern, the 'High-salt' and 'Refined grains' patterns were significantly associated with higher 10-year atherosclerotic cardiovascular disease risk score level (OR: 1.50, 95% CI: 1.02-2.21; OR: 1.92, 95% CI: 1.26-2.93) and 10-year ischemic cardiovascular disease risk score level (OR: 2.18, 95% CI: 1.25-3.80; OR: 2.64, 95% CI: 1.48-4.72) adjusted for gender, and behavioural and socioeconomic factors. The 'High-fat and salt' pattern was significantly associated with higher 10-year ischemic cardiovascular disease risk score level (OR: 1.97, 95% CI: 1.13-3.42). For underground workers, the 'High-salt' pattern was significantly associated with higher 10-year atherosclerotic cardiovascular disease risk score level (OR: 1.65, 95% CI: 1.16-2.36) and 10-year ischemic cardiovascular disease risk score level (OR: 1.76, 95% CI: 1.09-2.84). CONCLUSIONS: This study provides evidence for dietary patterns associated with higher 10-year cardiovascular disease risk score levels in Chinese miners, and facilitates relevant departments in designing effective dietary guidelines to ameliorate dietary structures.

High Strength and Deformation Mechanisms of Al0.3CoCrFeNi High-Entropy Alloy Thin Films Fabricated by Magnetron Sputtering.

Recently, high-entropy alloy thin films (HEATFs) with nanocrystalline structures and high hardness were developed by magnetron sputtering technique and have exciting potential to make small structure devices and precision instruments with sizes ranging from nanometers to micrometers. However, the strength and deformation mechanisms are still unclear. In this work, nanocrystalline Al0.3CoCrFeNi HEATFs with a thickness of ~4 µm were prepared. The microstructures of the thin films were comprehensively characterized, and the mechanical properties were systematically studied. It was found that the thin film was smooth, with a roughness of less than 5 nm. The chemical composition of the high entropy alloy thin film was homogeneous with a main single face-centered cubic (FCC) structure. Furthermore, it was observed that the hardness and the yield strength of the high-entropy alloy thin film was about three times that of the bulk samples, and the plastic deformation was inhomogeneous. Our results could provide an in-depth understanding of the mechanics and deformation mechanism for future design of nanocrystalline HEATFs with desired properties.

Dopa-Responsive Dystonia in Han Chinese Patients: One Novel Heterozygous Mutation in GTP Cyclohydrolase 1 (GCH1) and Three Known Mutations in TH.

BACKGROUND This study aimed to clarify the diagnosis and expand the understanding of dopa-responsive dystonia (DRD). MATERIAL AND METHODS Relevant data from clinical diagnoses and genetic mutational analyses in 3 Han Chinese patients with sporadic DRD were collected and analyzed. Protein structure/function was predicted. RESULTS One novel mutation of c.679A>G (p.T227A) in GCH1 and 3 known mutations of c.457C>T (p.R153X), c.739G>A (p.G247S), and c.698G>A (p.R227H) in tyrosine hydroxylase (TH) have been found and predicted to be damaging or deleterious. All of the mutations were localized in conserved sequences. The iterative threading assembly refinement (I-TASSER) server generated three-dimensional (3D) atomic models based on protein sequences from the novel nonsense mutation of c.679A>G (p.T227A) in GCH1, which showed that residue 227 was located in the GCH1 active site. CONCLUSIONS Patients carrying different non-synonymous variants had remarkable variation in clinical phenotype. This study expands the spectrum of genotypes and phenotypes of DRD in the Han Chinese ethnicity, provides new insights into the molecular mechanism of DRD, and helps the diagnosis and treatment of DRD.

Gold-catalyzed post-Ugi alkyne hydroarylation for the synthesis of 2-quinolones.

A series of propargylamides containing an electron-rich benzene ring was prepared through the Ugi reaction of 3,5-dimethoxyaniline with various propiolic acids, aldehydes and isocyanides. Subjecting these adducts to a gold-catalyzed intramolecular alkyne hydroarylation process allowed to efficiently construct the 2-quinolone core bearing a branched substituent on the nitrogen atom.

Inhibitory effects of 3α-hydroxy-lup-20(29)-en-23, 28-dioic acid on lipopolysaccharide-induced TNF-α, IL-1ß, and the high mobility group box 1 release in macrophages.

We investigated the anti-inflammatory effects of 3α-hydroxy-lup-20(29)-en-23, 28-dioic acid (HLEDA)-a lupane-type triterpene isolated from leaves of Acanthopanax gracilistylus W. W.Smith (AGS), as well as the underlying molecular mechanisms in lipopolysaccharide (LPS)-induced RAW264.7 cells. Our results demonstrated that HLEDA concentration-dependently reduced the production of nitric oxide (NO), significantly suppressed LPS-induced expression of TNF-α and IL-1ß at the mRNA and protein levels in RAW264.7 cells. Further analysis revealed that HLEDA could reduce the secretion of High Mobility Group Box 1 (HMGB1). Additionally, the results showed that HLEDA efficiently decreased nuclear factor-kappaB (NF-κB) activation by inhibiting the degradation and phosphorylation of IκBα. These results suggest that HLEDA exerts anti-inflammatory properties in LPS-induced macrophages, possibly through inhibition of the NF-κB signaling pathway, which mediates the expression of pro-inflammatory cytokines. These results warrant further studies that would concern candidate therapy for diseases, such as fulminant hepatitis and rheumatology of triterpenoids in AGS.