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Abstract Despite a lot of efforts devoted to construct efficient microbiomes, there are still major obstacles to moving from the lab to industrial applications due to the inapplicability of existing technologies or limited understanding of microbiome variation regularity. Here we show a domestication strategy to cultivate an effciient and resilient functional microbiome for addressing phenolic wastewater challenges, which involves directional domestication in shaker, laboratory water test in small-scale, gas test in pilot scale, water test in pilot scale, and engineering application in industrial scale. The domestication process includes the transition from water to gas, which provided complex transient environment for screening of a more adaptable and robust microbiome, thereby mitigating the performance disparities encountered when transitioning from laboratory experimentation to industrial engineering applications. Within the domestication and application processes for treating phenolic resin wastewater, a powerful functional microbiome was built by self-assembly. This leads to an augmented biodiversity and the development of more intricate phenol and formaldehyde metabolic pathways. The incorporation of increased stochastic processes and random network characteristics further suggested the stability of the microbial community during the application phase. This study elucidates the self-assembly process of microbial communities during the artificial construction process, showcasing their adaptive evolution under different adverse conditions. It serves as a noteworthy case study for the artificial construction of a microbiome for the engineering application of treating industrial wastewater.

In this paper, the microstructure and properties evolution of 93W-4.9Ni-2.1Fe alloy (93W, wt.%) and 30CrMnSiNi2A steel (wt.%) under different bonding times were studied with CrFeCoNiCu high entropy alloy (HEA) as the interlayer. The results show that a -Fe7W6 intermetallic compound layer is found in the diffusion zone between W particles and HEA at the 93W/HEA interface. The growth behavior and mechanism of μ layer were discussed. At the HEA/steel interface, rod-like Cr7C3 phase and nanoparticle Cr23C6 phase are formed in HEA due to the diffusion of C, which gradually coarsened and their content increased with the extension of bonding time. The tensile test shows that the maximum tensile strength of the joint reaches 592 MPa when the joint is kept at 950 °C for 1 h. The joint failure mode is the mixed fracture of μ phase, W particle and FCC solid solution.

ABSTRACT Aims Exploring fibrosis index‐4 (FIB‐4)'s predictive value for HBV‐related hepatocellular carcinoma (HCC) in assessing recurrence following stereotactic body radiation therapy (SBRT) in patients with HBV‐related HCC. Methods HBV‐related HCC patients who underwent SBRT were retrospectively enrolled from March 2012 to March 2020. Patients were divided into recurrence and non‐recurrence groups based on the HCC recurrence situation. Baseline data were collected from all patients before treatment and at 3 and 6 months after treatment, and FIB‐4 was calculated at the corresponding time points. Risk factors were selected using Cox regression. The FIB‐4 was stratified for survival analysis. Results One hundred and fifty‐two patients were included. With a mean age of 53.5 years old, 94.1% of them had liver cirrhosis. The median recurrence‐free survival (RFS) time for recurrent patients was 17.5 months. The tumor response rate of SBRT was 94.8%. HCC recurrence rates at 12, 24, 36, 48, and 60 months were 19.7% (30/152), 38.2% (58/152), 48.0% (73/152), 52.0% (79/152), and 53.3% (81/152), respectively. Cox regression showed that baseline FIB‐4 (95% CI: 1.030 ~ 1.144, p = 0.002) and 3 tumor nodules (95% CI: 3.727 ~ 260.663, p = 0.002) are risk factors for HCC recurrence. Patients with a baseline FIB‐4 > 6.55 were at a higher risk of HCC recurrence than those with a baseline FIB‐4

Background:Thyroid cancer (TC), the most prevalent endocrine malignancy, has been subjected to various treatment methods. However, the efficacy of asiaticoside (AC) for treating TC remains uncertain.Aims:To explore the impact of AC on TC and determine its potential mechanisms of action.Study Design:In vitro and in vivo cell line study.Methods:We evaluated the effects of AC on human TC cell lines, namely TPC-1 and FTC-133. Both in vitro and in vivo experimental validations were conducted.Results:AC significantly diminished the viability and proliferation of TC cells based on the CCK-8 assay and Edu staining findings. Migration and invasion assays revealed that AC effectively curtailed the migration and invasiveness of TC cells. The tube formation assay demonstrated that AC substantially impeded TC cell-induced angiogenesis. Western blot assay revealed that AC significantly reduced the expression levels of TRAF6, HIF-1α, and VEGFA, indicating that AC could potentially exert its anticancer effect by inhibiting the TRAF6/HIF1α pathway. Our in vivo experiments, which involved administering AC to BALB/c nude mice injected with TPC-1 cells, demonstrated significant inhibition of tumor growth and reduction in the expression of Ki-67, TRAF6, HIF-1α, and VEGFA.Conclusion:Our study highlights the significant inhibitory effect of AC on TC, offering fresh insights and potential drug candidates for TC treatment.

Atherosclerosis (AS) is recognized as a chronic inflammatory condition characterized by the accumulation of lipids and inflammatory cells within the damaged walls of arterial vessels. It is a significant independent risk factor for ischemic cardiovascular disease, ischemic stroke, and peripheral arterial disease. Despite the availability of current treatments such as statins, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, and lifestyle modifications for prevention, AS remains a leading cause of morbidity and economic burden worldwide. Thus, there is a pressing need for the development of new supplementary and alternative therapies or medications. Huangqin (Scutellaria baicalensis Georgi. [SBG]), a traditional Chinese medicine, exerts a significant immunomodulatory effect in AS prevention and treatment, with baicalin being identified as one of the primary active ingredients of traditional Chinese medicine. Baicalin offers a broad spectrum of pharmacological activities, including the regulation of immune balance, antioxidant and anti-inflammatory effects, and improvement of lipid metabolism dysregulation. Consequently, it exerts beneficial effects in both AS onset and progression. This review provides an overview of the immunomodulatory properties and mechanisms by which baicalin aids in AS prevention and treatment, highlighting its potential as a clinical translational therapy.

Objective To compare the effects of progestin-primed ovarian stimulation (PPOS) protocol and GnRH-a long protocol in infertility patients with normal ovarian reserve function undergoing invitro fertilization and embryo transfer.Methods A retrospective cohort study was conducted to analyze the clinical data of 2013 cycles of patients with normal ovarian reserve function who underwent invitro fertilization/intracytoplasmic sperm injection-embryo transfer (IVF/ICSI-ET) in the Department of Human Reproductive Center, Renmin Hospital, Hubei University of Medicine from January 2018 and June 2020. The PPOS protocol group included 679 cycles and GnRH-along protocol group included 1334 cycles, the pregnancy outcomes were compared between the two groups.Results The duration of Gn used and total Gn used dosage in the PPOS protocol group were less than those in the GnRH-along protocol group (Duration of Gn used: 10.05 ± 1.48 vs 11.90 ± 1.85 d, p 0.05); In addition, no severe OHSS occurred in the PPOS protocol group during ovulation induction, while 11 patients of severe ovarian hyperstimulation syndrome (OHSS) occurred in GnRH-a long protocol group (p

Sulfur-oxidizing bacteria play a crucial role in various processes, including mine bioleaching, biodesulfurization, and treatment of sulfur-containing wastewater. Nevertheless, the pathway involved in sulfur oxidation is highly intricate, making it complete comprehension a formidable and protracted undertaking. The mechanisms of sulfur oxidation within the Acidithiobacillus genus, along with the process of energy production, remain areas that necessitate further research and elucidation. In this study, a novel strain of sulfur-oxidizing bacterium, Acidithiobacillus Ameehan, was isolated. Several physiological characteristics of the strain Ameehan were verified and its complete genome sequence was presented in the study. Besides, the first genome-scale metabolic network model (AMEE_WP1377) was reconstructed for Acidithiobacillus Ameehan to gain a comprehensive understanding of the metabolic capacity of the strain.The characteristics of Acidithiobacillus Ameehan included morphological size and an optimal growth temperature range of 37-45°C, as well as an optimal growth pH range of pH 2.0-8.0. The microbe was found to be capable of growth when sulfur and K2O6S4 were supplied as the energy source and electron donor for CO2 fixation. Conversely, it could not utilize Na2S2O3, FeS2, and FeSO4·7H2O as the energy source or electron donor for CO2 fixation, nor could it grow using glucose or yeast extract as a carbon source. Genome annotation revealed that the strain Ameehan possessed a series of sulfur oxidizing genes that enabled it to oxidize elemental sulfur or various reduced inorganic sulfur compounds (RISCs). In addition, the bacterium also possessed carbon fixing genes involved in the incomplete Calvin-Benson-Bassham (CBB) cycle. However, the bacterium lacked the ability to oxidize iron and fix nitrogen. By implementing a constraint-based flux analysis to predict cellular growth in the presence of 71 carbon sources, 88.7% agreement with experimental Biolog data was observed. Five sulfur oxidation pathways were discovered through model simulations. The optimal sulfur oxidation pathway had the highest ATP production rate of 14.81 mmol/gDW/h, NADH/NADPH production rate of 5.76 mmol/gDW/h, consumed 1.575 mmol/gDW/h of CO2, and 1.5 mmol/gDW/h of sulfur. Our findings provide a comprehensive outlook on the most effective cellular metabolic pathways implicated in sulfur oxidation within Acidithiobacillus Ameehan. It suggests that the OMP (outer-membrane proteins) and SQR enzymes (sulfide: quinone oxidoreductase) have a significant impact on the energy production efficiency of sulfur oxidation, which could have potential biotechnological applications.

Abstract To explore temporal and spatial effects on the planktonic prokaryotic community composition (PCC) in the coastal region of the Bohai Sea, surface water samples were collected from 12 to 28 regularly distributed sites in Bohai Bay across 3 months from different seasons to characterize the PCC using high-throughput sequencing of the 16S rRNA V4 region. Prokaryotic α- and β-diversity showed significant temporal variation during the three sampling months. VPA analysis based on both weighted and unweighted UniFrac distances exhibited a shift of environmental and spatial effects on PCC variation with temporal variation. Quantification analysis of assembly processes on community turn over showed that “heterogeneous selection” dominated for PCC temporal variation, with basic abiotic parameters such as temperature, pH, ammonia nitrogen as the driving factors. Analysis of seasonal features showed that seasonal specific OTUs (ssOTUs) exhibited different seasonal attributions under the same phylum; meanwhile, the ssOTUs showed significant correlations with the driving environmental factors, which suggested that finer-level analysis was needed to more strictly reflect the temporal variation. Moreover, predicted nitrogen and sulfur metabolism were significantly shifted during the temporal variation. Our results clearly showed that seasonally varied environmental factors drive the “heterogeneous selection” process for PCC assembly in seawaters of Bohai Bay during different sampling seasons.

Abstract Background The gonadotropin-releasing hormone agonist (GnRH-a) has been used in in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycles for a long time. This paper evaluates the efficacy and safety of two commonly used protocols (follicular-phase depot GnRH-a protocol and daily mid-luteal long GnRH-a protocol) in normal responders undergoing IVF/ICSI using propensity score matching (PSM) analysis. Methods A total of 6,816 infertile women treated within the period from January 2016 to September 2020 were stratified into cohorts. A total of 2,851 patients received the long-acting group (depot GnRH-a protocol), and 1,193 used the short-acting group (long GnRH-a protocol) after the data-selection process. PSM was utilized for sampling by up to 1:1 nearest neighbour matching to adjust the numerical difference and balance the confounders between groups. The primary outcome was the live birth rate (LBR). Multivariable logistic analysis was used to evaluate the difference between these two protocols in relation to the LBR. Result(s) In this study, 1:1 propensity score matching was performed to create a perfect match of 964 patients in each group. After matching, the blastocyst formation rates, oestradiol (E2) value on Day hCG + 9, progesterone (P) value on Day hCG + 9, implantation rates, clinical pregnancy rates, and LBR were more favourable in the depot GnRH-a protocol than in the long GnRH-a protocol (P

While self-healing catalysts may survive the harsh environments used for oxygen evolution, understanding how to develop such electrocatalysts remains a challenge. Here, authors find cobalt to promote the self-healing of leached iron centers in borate-intercalated nickel-iron-cobalt oxyhydroxides.

Objectives: To investigate the factors and virological significance of serum hepatitis B virus (HBV) pregenomic RNA (pgRNA) status after long-term antiviral therapy with nucleos(t)ide analogues (NAs) in patients with chronic hepatitis B (CHB). Methods: In total, 51 treatment-naïve patients with CHB were included in the study. Clinical data were collected at baseline, during 5 years and at year 10 of NA treatment. Serum HBV pgRNA status of 51 patients was determined at year 5. Results: At year 5, 45% of the patients remained positive for HBV pgRNA. There were significant differences in baseline hepatitis B e antigen (HBeAg) status, HBV DNA load and hepatitis B surface antigen (HBsAg) levels between patients testing positive and negative for HBV pgRNA at year 5. Serum HBV pgRNA status and serum HBV DNA load were correlated after 5 years of NA treatment (r = 0.347, P = 0.013). Being HBV pgRNA positive at year 5 was an independent risk factor for sustainedly undetectable HBV DNA after 10 years of NA treatment (odds ratio 13.638, 95% confidence interval 1.32–140.81; P = 0.028). Furthermore, HBV pgRNA status at year 5 was associated with HBV DNA re-appearance at year 10 (P = 0.009). Conclusions: HBV pgRNA status at year 5 can reveal HBV covalently closed circular DNA (cccDNA) activity, and HBV pgRNA positivity after long-term antiviral therapy may indicate higher transcriptional activity of HBV cccDNA. Long-term dynamic monitoring of HBV pgRNA should be considered.

We theoretically investigate the non-sequential double ionization of Ar atoms in the combined fields of linearly polarized laser and circularly polarized laser through 3D semiclassical simulations. By partially overlapping the two time-delayed multicycle laser pulses, we construct an optical waveform whose polarization ellipticity increase slowly for consecutive optical cycles. This composite laser pulses with the time-dependent ellipticity can tunnel-ionize atoms and steer the first tunneling electron to recollision with the second bound electron through different trajectories, in which the recollision occurs with different return times of the first ionized electron. Through tuning delay time between the two laser pulses, the double ionization yields and recollision trajectories with different return times can be controlled. The time-dependent ellipticity with different delay time can enhance or suppress the probability of different return times. This work provides a scheme exploring electron dynamics in few optical cycle or even subcycle time scale in a multicycle laser field without having to be limited to near-single-cycle laser pulses.

With the looming goal of carbon neutrality and increasingly stringent environmental protection policies, gas purification in coal-fired power plants is becoming more and more intense. To achieve the NOx emission standard when coal-fired power plants are operating at full load, wide-temperature denitrification catalysts that can operate for a long time in the range of 260–420°C are worthy of study. This review focuses on the research progress and deactivation mechanism of selective catalytic reduction (SCR) denitration catalysts applied to a wide temperature range. With the increasing application of SCR catalysts, it also means that a large amount of spent catalysts is generated every year due to deactivation. Therefore, it is necessary to recycle the wide temperature SCR denitration catalyst. The challenges faced by wide-temperature SCR denitration catalysts are summarized by comparing their regeneration processes. Finally, its future development is prospected.

ObjectiveThe role of stereotactic body radiation therapy (SBRT) for treating small hepatocellular carcinoma (sHCC) has gained increasing recognition. However, the prognosis and risk factors for recurrence in patients with sHCC remain unclear. This study investigated the risk factors for the recurrence of hepatitis B virus (HBV)-related sHCC after SBRT.MethodsA total of 240 HBV-related sHCC patients treated with SBRT between March 2011 and March 2020 were retrospectively analyzed. The cumulative probability of recurrence was calculated according to the Kaplan–Meier method. Univariate and multivariate analyses were performed with Cox proportional hazard models.ResultsRecurrent hepatocellular carcinoma developed in 134 (55.8%) patients at a median time of 27 months after SBRT. The one- and two-year rates of recurrence were 20.9 and 45.0%, respectively. The median follow-up time was 30 months. The Cox multivariate analysis indicated that age (P = 0.029, HR [1.019, 1.002–1.037]), tumor size (P = 0.012, HR [1.227, 1.045–1.440]), and aspartate aminotransferase-to-platelet ratio index (APRI) (P = 0.005, HR [1.911, 1.221–2.989]) were independent risk factors for recurrence.ConclusionPatients receiving SBRT for HBV-related sHCC may be at greater risk of recurrence if they have a high APRI score combined with advanced age and large tumor size.

Nuclear localization of cytoplasmic RNA virus proteins mediated by intrinsic nuclear localization signal (NLS) plays essential roles in successful virus replication. We previously reported that NLS mutation in the matrix (M) protein obviously attenuates the replication and pathogenicity of Newcastle disease virus (NDV), but the attenuated replication mechanism remains unclear. In this study, we showed that M/NLS mutation not only disrupted M’s nucleocytoplasmic trafficking characteristic but also impaired viral RNA synthesis and transcription. Using TMT-based quantitative proteomics analysis of BSR-T7/5 cells infected with the parental NDV rSS1GFP and the mutant NDV rSS1GFP-M/NLSm harboring M/NLS mutation, we found that rSS1GFP infection stimulated much greater quantities and more expression changes of differentially expressed proteins involved in host cell transcription, ribosomal structure, posttranslational modification, and intracellular trafficking than rSS1GFP-M/NLSm infection. Further in-depth analysis revealed that the dominant nuclear accumulation of M protein inhibited host cell transcription, RNA processing and modification, protein synthesis, posttranscriptional modification and transport; and this kind of inhibition could be weakened when most of M protein was confined outside the nucleus. More importantly, we found that the function of M protein in the cytoplasm effected the inhibition of TIFA expression in a dose-dependent manner, and promoted NDV replication by down-regulating TIFA/TRAF6/NF-κB-mediated production of cytokines. It was the first report about the involvement of M protein in NDV immune evasion. Taken together, our findings demonstrate that NDV replication is closely related to the nucleocytoplasmic trafficking of M protein, which accelerates our understanding of the molecular functions of NDV M protein.

Abstract Background Lipid profiles are declined in patients with viral liver cirrhosis and correlated with severity of liver disease. Hepatitis B virus (HBV) is the leading cause of liver cirrhosis in China. Our primary aim was to investigate whether serum lipids and lipoproteins associate with survival in patients with HBV-related cirrhosis and acute gastrointestinal bleeding, and develop a 6-week mortality risk score that incorporates it. Methods From January 2008 to December 2015, consecutive cirrhotic patients with acute gastrointestinal bleeding admitted to our hospital were evaluated and randomly divided into the derivation (n = 629) and validation (n = 314) cohorts. A logistic regression model was established to confirm the association between lipoprotein cholesterol and mortality. Accuracy to predict mortality were assessed by area under the receiver operating characteristic curves (AUROCs) and compared using the Hanley and McNeil test. Results Among study subjects, the 6-week mortality rate was 10.6%. High-density lipoprotein cholesterol (HDL-C) level was found to correlate most strongly with prognostic scores. On ROC analysis, HDL-C showed excellent diagnostic accuracy for 6-week mortality. Logistic regression analysis provided a simple algorithm based on the combined use of 4 variables (total bilirubin (TBIL), HDL-C, International normalized ratio, and hemoglobin), allowing accurate discrimination of 3 distinct prognostic subgroups with 1.7% (low risk), 12.3% (intermediate risk), and 56.9% (high risk) mortality. Its accuracy was significantly better than that of Child–Pugh, model of end-stage liver disease, albumin-bilirubin score, D’Amico model, Augustin model, AIMS65 score and Glasgow-Blatchford score. Baseline HDL-C values ≤ 0.54 mmol/L were associated with markedly lower 6-week survival. Comparable results were found in the validation set. Conclusion HDL-C is a potential indicator for the prognosis of patients with cirrhosis and acute gastrointestinal bleeding. The new algorithm based on HDL-C allowed an accurate predictive assessment of 6-week mortality after bleeding attack.

Abstract Bromodomain-containing protein 2 (BRD2) is a nucleus-localized serine-threonine kinase that plays pivotal roles in the transcriptional control of diverse genes. In our previous study, the chicken BRD2 (chBRD2) protein was found to interact with the Newcastle disease virus (NDV) matrix (M) protein using a yeast two-hybrid screening system, but the role of the chBRD2 protein in the replication of NDV remains unclear. In this study, we first confirmed the interaction between the M protein and chBRD2 protein using fluorescence co-localization, co-immunoprecipitation and pull-down assays. Intracellular binding studies indicated that the C-terminus (aa 264–313) of the M protein and the extra-terminal (ET) domain (aa 619–683) of the chBRD2 protein were responsible for interactions with each other. Interestingly, although two amino acids (T621 and S649) found in the chBRD2/ET domain were different from those in the human BRD2/ET domain and in that of other mammals, they did not disrupt the BRD2-M interaction or the chBRD2-M interaction. In addition, we found that the transcription of the chBRD2 gene was obviously decreased in both NDV-infected cells and pEGFP-M-transfected cells in a dose-dependent manner. Moreover, small interfering RNA-mediated knockdown of chBRD2 or overexpression of chBRD2 remarkably enhanced or reduced NDV replication by upregulating or downregulating viral RNA synthesis and transcription, respectively. Overall, we demonstrate for the first time that the interaction of the M protein with the chBRD2 protein in the nucleus promotes NDV replication by downregulating chBRD2 expression and facilitating viral RNA synthesis and transcription. These results will provide further insight into the biological functions of the M protein in the replication of NDV.

BackgroundPolyene phosphatidylcholine (PPC) has been widely used to treat liver diseases in China. However, there is a lack of post-marketing evidence demonstrating its liver-protective efficiency among patients infected with hepatitis B virus (HBV). This study analyzed the multicenter real-world data to compare the effectiveness of PPC with those of magnesium isoglycyrrhizinate (IsoMag) and glutathione (GSH) in patients with liver injury.MethodsThis study comprised the real-world data analysis of a multicenter, retrospective observational cohort. The data were retrieved from the Cooperative Registry of the Hospital Prescription in China between 1 October 2018, and 30 September 2019. A growth curve analysis was performed to compare the effects of different treatments on liver function longitudinally for up to 30 days after treatment commencement. In addition, the dose effect of the PPC treatment was investigated.ResultsThe final cohort included 6,052 patients with approximately 8% infected with HBV (N = 471). There were 1,649, 1,750, and 2,653 patients in the PPC, GSH, and IsoMag groups, respectively, with an average age of 53.9 years. In patients with HBV infection, the PPC treatment was associated with a significant decline in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels (slopes: −3.7, 95% CI, −6.0 to −1.5 U/L/day; −2.4, 95% CI, −4.5 to −0.3 U/L/day, respectively). However, there were no significant differences in the effects among the three groups. In patients without HBV infection, the PPC treatment decreased ALT, AST, γ-glutamyl transferase (GGT), and albumin levels (−5.2, 95% CI, −5.8 to −4.5 U/L/day; −3.5, 95% CI, −4.2 to −2.7 U/L/day; −4.9, 95% CI, −6.2 to −3.7 U/L/day, −0.07, 95% CI, −0.09 to −0.04 g/L/day, respectively) and showed a stronger effect on lowering ALT levels than GSH (−2.6, 95% CI, −3.3 to −1.8 U/L/day, p < 0.05), as well as a stronger effect on lowering GGT levels than IsoMag (−1.4, 95% CI, −2.4 to −0.4 U/L/day, p < 0.05). PPC had no impact on prothrombin activity levels in patients with or without HBV infection. High-dose PPC exhibited a stronger effect on lowering ALT and AST levels than low-dose PPC.ConclusionThis was the first real-world multicenter study to demonstrate that PPC efficiently lowers ALT and AST levels in patients with liver diseases regardless of the status of HBV infection. PPC treatment showed a comparable or better effect compared with GSH and IsoMag treatments. High-dose PPC resulted in a stronger effect than low-dose PPC.

Serum hepatitis B virus pregenomic RNA (HBV pgRNA) is a potential biomarker that is correlated with covalently closed circular DNA. The long-term dynamics of HBV pgRNA in patients with chronic hepatitis B need to be explored. One hundred naïve nucleos(t)ide analog-treated patients with chronic hepatitis B were enrolled to analyze the dynamics of HBV pgRNA over 9 years. The positive rates of HBV pgRNAs declined gradually and showed biphasic kinetics. Serum HBV pgRNA levels in patients treated with entecavir became negative later than those treated with adefovir or lamivudine. Patients who remain positive for HBV pgRNA after 9 years of treatment may have higher viral transcription efficiencies. The reverse transcription efficiency of hepatitis B e-antigen (HBeAg)-positive patients was higher than that of HBeAg-negative patients at baseline and showed no difference after 24-week nucleos(t)ide analog treatment. The trajectory of serum HBV pgRNA-negative transformation differs in patients with different characteristics. Long-term dynamic monitoring of serum HBV pgRNA levels has significance in hepatitis B treatment.

This paper presents an in-depth study of the variable reference process to improve the organization and properties of selective laser melting TC4 specimens. A relationship equation between body energy density and stratification is proposed. This study aimed to look into how layer and volume energy density affect the surface, tensile characteristics, and microstructure of specimens. The test findings demonstrated that specimen densities rise as the power index falls, with the most excellent density reaching 99.42%. The number of secondary α’ phases declined as the energy density of the laminae slowed down. The tensile strength of these specimens reached 1190.84 MPa, and the yield strength came at 1103.87 MPa with the same interval of variable laser power. This offers a fresh avenue for research into SLM to enhance the specimens’ overall performance.

The study of two-dimensional (2D) superconductors is one of the most prominent areas in recent years and has remained a long-standing scientific challenge. Since the introduction of the new member of 2D material family consisting of transition-metal elements with Borides (MBenes), the study of various properties of 2D metal borides has attracted widespread interest. In this work, we systematically investigate the phonon-mediated superconductivity in 2D M B _4 ( M = V, Nb, and Ta), by using the first-principles calculations. Starting from the dynamical stabilities of these structures, we perform a detailed analysis of the electron–phonon coupling and superconductivity of AB-stacked MBenes by solving the anisotropic Eliashberg equation. NbB _4 has the largest electron–phonon coupling and the highest superconducting transition temperature T _c of 35.4 K. Our study broadens the 2D superconducting boride family, which is of great significance for the study of 2D superconductivity.

The flame dynamics of steady propagation of a premixed flame in semi-closed channels is investigated. The hydrodynamic model takes into account impacts of channel width, thermal expansion, straining effect, and downward gravity force on the flame front. The steady flame shape and its velocity field could be determined by numerical iteration of a weakly nonlinear front equation and linearized governing equations with Fourier transform, respectively. Results reveal that the introduction of thermal expansion and gravity force enhance the flame curvature and increase the burning velocity, while the straining effect suppresses the flame bending processes. In addition, a non-monotonic dependence of the burning velocity on the Peclet number is further demonstrated. It reveals that the thermal expansion and strain effect would have impacts on the burning velocity as well.

Metal matrix composites (MMCs) incorporate a reinforcing or functional secondary phase into a metal matrix to achieve specific properties. Of the parameters which may affect the mechanical behavior of MMCs, the structure and properties of the reinforcement/matrix interface play a crucial role. This article reviews recent developments in measuring the interfacial properties in advanced MMCs, with an emphasis on the use of micro-/nano-mechanical testing approaches. It is shown that, with the novel in situ and ex situ experimental capability, researchers can now obtain some of the critical interfacial properties as well as the effects of reinforcement/matrix interfaces on the composites' deformation and failure mechanisms that were unattainable previously by conventional methodologies. Moreover, the micro-/nano-mechanical testing platform allows for both fundamental and applied research on the composites’ mechanical performance under service conditions, which is considered a promising and emerging research direction.

Abstract Many reports have shown that the composition of the bacterioplankton community can serve as a biological indicator to evaluate the occurrence of shrimp diseases. However, the distribution, diversity, and function of planktonic actinobacteria in shrimp ponds are still poorly understood. In this study, a prototype of a 16S rRNA gene-based taxonomic microarray was developed and evaluated for monitoring of planktonic actinobacteria in shrimp ponds. The prototype microarray is composed of 30 probes that target ten dominant families of planktonic actinobacteria found in shrimp ponds. The specificity of the actinobacterial microarray was validated by a set of control hybridizations with 16S rRNA genes clones. The prototype microarray was subsequently tested with two seawater samples from ponds with diseased shrimp populations (PDS) and ponds with healthy shrimp populations (PHS). The actinobacteria hybridization profiles revealed a lower abundance of Microbacteriaceae and a higher abundance of Mycobacteriaceae in PDS than in PHS. The changes in planktonic actinobacterial communities were validated by pyrosequencing data. These results support the utility of the microarray for monitoring planktonic actinobacteria in shrimp ponds and aquaculture environments.

Post-operative cognitive dysfunction (POCD) could cause short-term or long-term cognitive disruption lasting weeks or months after anesthesia and surgery in elderly. However, no effective treatment of POCD is currently available. Previous studies indicated that the enhancement of brain-derived neurotrophic factor (BDNF) expression, and the elevation the cholinergic system, might be effective to prevent POCD. In this study, we have discovered that tacrine(10)-hupyridone (A10E), a novel acetylcholinesterase (AChE) inhibitor derived from tacrine and huperzine A, could prevent surgery-induced short-term and long-term impairments of recognition and spatial cognition, as evidenced by the novel object recognition test and Morris water maze (MWM) tests, in aged mice. Moreover, A10E significantly increased the expression of BDNF and activated the downstream Akt and extracellular regulated kinase (ERK) signaling in the surgery-treated mice. Furthermore, A10E substantially enhanced choline acetyltransferase (ChAT)-positive area and decreased AChE activity, in the hippocampus regions of surgery-treated mice, indicating that A10E could prevent surgery-induced dysfunction of cholinergic system, possibly via increasing the synthesis of acetylcholine and the inhibition of AChE. In conclusion, our results suggested that A10E might prevent POCD via the activation of BDNF pathway and the inhibition of AChE, concurrently, in aged mice. These findings also provided a support that A10E might be developed as a potential drug lead for POCD.

Rhynchophylline is a major tetracyclic oxindole alkaloid in Uncaria rhynchophylla, which has been extensively used as traditional herb medicine for the prevention of convulsions and hypertension. However, there is still little evidence about the neuroprotective effects of rhynchophylline for Parkinson’s disease (PD), a neurodegenerative condition currently without any effective cure. In this present study, the neuroprotective molecular mechanisms of rhynchophylline were investigated in a cellular model associated with PD. It is shown that rhynchophylline (10–50 μM) greatly prevented neurotoxicity caused by 1-methyl-4-phenylpyridinium ion (MPP+) in primary cerebellar granule neurons, as evidenced by the promotion of cell viability as well as the reversal of dysregulated protein expression of Bax/Bcl-2 ratio. Very encouragingly, we found that rhynchophylline markedly enhanced the activity of the transcription factor myocyte enhancer factor 2D (MEF2D) at both basal and pathological conditions using luciferase reporter gene assay, and reversed the inhibition of MEF2D caused by MPP+. Additionally, pharmacological inhibition of PI3-Kinase or short hairpin RNA-mediated gene down-regulation of MEF2D abrogated the protection provided by rhynchophylline. Furthermore, Western blot analysis revealed that rhynchophylline could potentiate PI3-K/Akt to attenuate GSK3β (the MEF2D inhibitor) in response to MPP+ insult. In conclusion, rhynchophylline inhibits MPP+-triggered neurotoxicity by stimulating MEF2D via activating PI3-K/Akt/GSK3β cascade. Rhynchophylline is served as a novel MEF2D enhancer and might be a potential candidate for further preclinical study in the prevention of PD.

Lycii Cortex (LyC) is widely used as a traditional anti-ageing food ingredient in soup, congee and tea for preventing degenerative disease. However, its bioactive components and modes of action have never been characterized scientifically. The aims of this study are to: 1) examine the neuroprotective effects of LyC against oxidative stress; 2) identify the bioactive components; 3) elucidate the possible molecular mechanisms of the key components. Phytochemical profiling using LC–MS/MS revealed that 7-(4-amino-butoxy)-6-methoxycoumarin, kukoamines A and B, and lyciumins A and B are the major characteristic compounds in LyC. LyC crude extract and kukoamines were effective in preventing cell damage in the H2O2-induced primary cerebellar granule neurons (CGNs) model, but kukoamines were more efficacious and potent than the extract. Western blot analysis revealed that KB, the most abundant kukoamine, was capable of inhibiting the neuronal apoptosis via activating the PI3-K/Akt/GSK3β pathway. Thus, our explorative results indicated that kukoamine, the major compounds in LyC, acts as a promising neuroprotectant against the H2O2 induced toxicity in CGNs model via activating the PI3-K/Akt/GSK3β pathway. Furthermore, molecular insight to substantiate the application of LyC or kukoamines for prevention and treatment of neurodegenerative diseases in which oxidative stress is involved is demonstrated.

The over-activation of NMDA receptor via the excessive glutamate is believed to one of the most causal factors associated with Alzheimer’s disease (AD), a progressive neurodegenerative brain disorder. Molecules that could protect against glutamate-induced neurotoxicity may hold therapeutic values for treating AD. Herein, the neuroprotective mechanisms of dimeric DT-010, a novel derivative of naturally occurring danshensu and tetramethylpyrazine, were investigated using primary rat cerebellar granule neurons (CGNs) and hippocampal neurons. It was found that DT-010 (3–30 μM) markedly prevented excitotoxicity of CGNs caused by glutamate, as evidenced by the promotion of neuronal viability as well as the reversal of abnormal morphological changes. While its parent molecules did not show any protective effects even when their concentration reached 50 μM. Additionally, DT-010 almost fully blocked intracellular accumulation of reactive oxygen species caused by glutamate and exogenous oxidative stimulus. Moreover, Western blot results demonstrated that DT-010 remarkably attenuated the inhibition of pro-survival PI3K/Akt/GSK3β pathway caused by glutamate. Ca2+ imaging with Fluo-4 fluorescence analysis further revealed that DT-010 greatly declined glutamate-induced increase in intracellular Ca2+. Most importantly, with the use of whole-cell patch clamp electrophysiology, DT-010 directly inhibited NMDA-activated whole-cell currents in primary hippocampal neurons. Molecular docking simulation analysis further revealed a possible binding mode that inhibited NMDA receptor at the ion channel, showing that DT-010 favorably binds to Asn602 of NMDA receptor via arene hydrogen bond. These results suggest that DT-010 could be served as a novel NMDA receptor antagonist and protect against glutamate-induced excitotoxicity from blocking the upstream NMDA receptors to the subsequent Ca2+ influx and to the downstream GSK3β cascade.

Indirubins are natural occurring alkaloids extracted from indigo dye-containing plants. Indirubins could inhibit various kinases, and might be used to treat chronic myelocytic leukemia, cancer and neurodegenerative disorders. 7-bromoindirubin-3-oxime (7Bio), an indirubin derivative derived from indirubin-3-oxime, possesses inhibitory effects against cyclin-dependent kinase-5 (CDK5) and glycogen synthase kinase-3β (GSK3β), two pharmacological targets of Alzheimer's disease (AD). In this study, we have discovered that 2.3–23.3 μg/kg 7Bio effectively prevented β-amyloid (Aβ) oligomer-induced impairments of spatial cognition and recognition without affecting bodyweight and motor functions in mice. Moreover, 7Bio potently inhibited Aβ oligomer-induced expression of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). Furthermore, 7Bio significantly prevented the decreased expression of synapsin-1 and PSD-95, biomarkers of pre-synaptic and post-synaptic proteins in Aβ oligomer-treated mice. The mean optical density (OD) with hyper-phosphorylated tau (pTau), glial fibrillary acidic protein (GFAP) and CD45 positive staining in the hippocampus of 7Bio-treated mice were significantly decreased compared to those of Aβ oligomer-treated mice. In addition, Western blotting analysis showed that 7Bio attenuated Aβ oligomer-decreased expression of pSer9-GSK3β. Those results suggested that 7Bio could potently inhibit Aβ oligomer-induced neuroinflammation, synaptic impairments, tau hyper-phosphorylation, and activation of astrocytes and microglia, which may contribute to the neuroprotective effects of 7Bio. Based on these findings, we expected that 7Bio might be developed as a novel anti-AD lead compound.

As a complex system, the complicated interactions between chemical ingredients, as well as the potential rules of interactive associations among chemical ingredients of traditional Chinese herbal formulae are not yet fully understood by modern science. On the other hand, network analysis is emerging as a powerful approach focusing on processing complex interactive data. By employing network approach in selected Chinese herbal formulae for the treatment of coronary heart disease (CHD), this article aims to construct and analyze chemical ingredients network of herbal formulae, and provide candidate herbs, chemical constituents, and ingredient groups for further investigation. As a result, chemical ingredients network composed of 1588 ingredients from 36 herbs used in 8 core formulae for the treatment of CHD was produced based on combination associations in herbal formulae. In this network, 9 communities with relative dense internal connections are significantly associated with 14 kinds of chemical structures with P

We have previously synthesized a series of hybrid compounds by linking ferulic acid to tacrine as multifunctional agents based on the hypotheses that Alzheimer's disease (AD) generates cholinergic deficiency and oxidative stress. Interestingly, we found that they may have potential pharmacological activities for treating AD. Here we report for the first time that tacrine-6-ferulic acid (T6FA), one of these compounds, can prevent amyloid-β peptide (Aβ)-induced AD-associated pathological changes in vitro and in vivo. Our results showed that T6FA significantly inhibited auto- and acetylcholinesterase (AChE)-induced aggregation of Aβ(1-40)in vitro and blocked the cell death induced by Aβ(1-40) in PC12 cells. In an AD mouse model by the intracerebroventricular injection of Aβ(1-40), T6FA significantly improved the cognitive ability along with increasing choline acetyltransferase and superoxide dismutase activity, decreasing AChE activity and malondialdehyde level. Based on our findings, we conclude that T6FA may be a promising multifunctional drug candidate for AD.

SU5416 was originally designed as a potent and selective inhibitor of vascular endothelial growth factor receptor-2 (VEGFR-2) for cancer therapy. In this study, we have found for the first time that SU5416 unexpectedly prevented 1-methyl-4-phenylpyridinium ion (MPP(+))-induced neuronal apoptosis in cerebellar granule neurons, and decreased 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced loss of dopaminergic neurons and impairment of swimming behavior in zebrafish in a concentration-dependent manner. However, VEGFR-2 kinase inhibitor II, another specific VEGFR-2 inhibitor, failed to reverse neurotoxicity at the concentration exhibiting anti-angiogenic activity, strongly suggesting that the neuroprotective effect of SU5416 is independent from its anti-angiogenic action. SU5416 potently reversed MPP(+)-increased intracellular nitric oxide level with an efficacy similar to 7-nitroindazole, a specific neuronal nitric oxide synthase (nNOS) inhibitor. Western blotting analysis showed that SU5416 reduced the elevation of nNOS protein expression induced by MPP(+). Furthermore, SU5416 directly inhibited the enzyme activity of rat cerebellum nNOS with an IC(50) value of 22.7 µM. In addition, knock-down of nNOS expression using short hairpin RNA (shRNA) abolished the neuroprotective effects of SU5416 against MPP(+)-induced neuronal loss. Our results strongly demonstrate that SU5416 might exert its unexpected neuroprotective effects by concurrently reducing nNOS protein expression and directly inhibiting nNOS enzyme activity. In view of the capability of SU5416 to cross the blood-brain barrier and the safety for human use, our findings further indicate that SU5416 might be a novel drug candidate for neurodegenerative disorders, particularly those associated with NO-mediated neurotoxicity.

Miracle fruit (Synsepalum dulcificum) belongs to the Sapotaceae family. It can change flavors on taste buds, transforming acidic tastes to sweet. We evaluated various miracle fruit extracts, including water, butanol, ethyl acetate (EA), and hexane fractions, to determine its antioxidant effects. These extracts isolated from miracle fruit exerted potential for reduction of uric acid and inhibited xanthine oxidase activity in vitro and in monosodiumurate (MSU)-treated RAW264.7 macrophages. Moreover, we also found that the butanol extracts of miracle fruit attenuated oxonic acid potassium salt-induced hyperuricaemia in ICR mice by lowering serum uric acid levels and activating hepatic xanthine oxidase. These effects were equal to those of allopurinol, suggesting that the butanol extract of miracle fruit could be developed as a novel anti-hyperuricaemia agent or health food.

Pardaxin (H-GFFALIPKIISSPLFKTLLSAVGSALSSSGGQE-OH), a 33-amino-acid polypeptide, is an antimicrobial peptide (AMP) isolated from the marine fish species Pardachirus marmoratus. Pardaxin shows antibacterial and antitumor activities. However, pardaxin-induced inhibition of oral cancer and the mechanism of tumor reduction in buccal pouch carcinogenesis after pardaxin painting remain undetermined. Additionally, the toxic effects of pardaxin on normal tissue remain unclear. The present study investigated the anticancer activity of pardaxin in oral squamous cell carcinoma (OSCC) cells in the hamster buccal pouch model with or without 7,12-dimethylbenz[a]anthracene (DMBA) pretreatment. This is the first study to confirm the effects of pardaxin on normal tissue and its nontoxic effects in vivo. Cell viability assays and colony formation tests in OSCC cell lines (SCC-4) demonstrated that pardaxin reduced cell viability in a dose-dependent manner. Immunofluorescence staining of cleaved caspase-3 in SCC-4 cells revealed that expression of activated caspase-3 in SCC-4 cells significantly increased after 24-h treatment with pardaxin. Additionally, a cell cycle analysis indicated that pardaxin treatment resulted in the cell cycle arrest of SCC-4 cells in the G2/M phase, thereby limiting cell proliferation. Furthermore, pardaxin treatment substantially alleviated carcinogenesis in the DMBA-induced hamster buccal pouch model by lowering prostaglandin E2 levels. These results suggest that pardaxin is a potential marine drug for adjuvant chemotherapy for human OSCC and oral cancer.